U.S. patent application number 14/678550 was filed with the patent office on 2016-08-18 for system and method for the detection of gamma radiation from a radioactive analyte.
This patent application is currently assigned to Lucerno Dynamics, LLC. The applicant listed for this patent is Joshua G. Knowland, Ronald K. Lattanze, Charles W. Scarantino. Invention is credited to Joshua G. Knowland, Ronald K. Lattanze, Charles W. Scarantino.
Application Number | 20160238716 14/678550 |
Document ID | / |
Family ID | 54190021 |
Filed Date | 2016-08-18 |
United States Patent
Application |
20160238716 |
Kind Code |
A9 |
Knowland; Joshua G. ; et
al. |
August 18, 2016 |
SYSTEM AND METHOD FOR THE DETECTION OF GAMMA RADIATION FROM A
RADIOACTIVE ANALYTE
Abstract
A system and method for the measurement of radiation emitted
from an in-vivo administered radioactive analyte. Gamma radiation
sensors may be used to determine the proper or improper
administration of a radioactive analyte in some cases, the system
employs a sensor having a scintillation material to convert gamma
radiation to visible light, which enables embodiments of the sensor
to be ex vivo. A light detector converts the visible light to an
electrical signal. This signal is amplified and is processed to
measure the captured radiation. Temperature of the sensor may be
recorded along with this radiation measurement for temperature
compensation of ex vivo embodiments. The sensor enables collection
of sufficient data to support separate application to predictive
models, background comparisons, or change analysis.
Inventors: |
Knowland; Joshua G.; (Cary,
NC) ; Scarantino; Charles W.; (Raleigh, NC) ;
Lattanze; Ronald K.; (Morrisville, NC) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Knowland; Joshua G.
Scarantino; Charles W.
Lattanze; Ronald K. |
Cary
Raleigh
Morrisville |
NC
NC
NC |
US
US
US |
|
|
Assignee: |
Lucerno Dynamics, LLC
Raleigh
NC
|
Prior
Publication: |
|
Document Identifier |
Publication Date |
|
US 20150276937 A1 |
October 1, 2015 |
|
|
Family ID: |
54190021 |
Appl. No.: |
14/678550 |
Filed: |
April 3, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
13840925 |
Mar 15, 2013 |
9002438 |
|
|
14678550 |
|
|
|
|
61653014 |
May 30, 2012 |
|
|
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 6/467 20130101;
G01T 1/161 20130101; A61B 6/463 20130101; G01T 1/1612 20130101;
G01T 1/1648 20130101; A61B 6/4258 20130101 |
International
Class: |
G01T 1/161 20060101
G01T001/161; A61B 6/00 20060101 A61B006/00; A61B 6/03 20060101
A61B006/03 |
Claims
1. A system for the ex vivo real-time detection of gamma radiation
emitted by a subject from administration and uptake over a period
of time of a radioactive analyte that decays in vivo by positron
emission, the system comprising: at least one ex vivo measurement
sensor having a sensor housing, a scintillation material, a light
detector, a temperature sensor, a signal amplifier, and a sensor
power source, the light detector, temperature sensor, signal
amplifier, and sensor power source in operable communication, the
scintillation material and light detector disposed within the
sensor housing in a light proof manner, with the scintillation
material adapted to receive a level of gamma radiation over the
period of time from the in vivo radioactive analyte and to emit
photons representative of the gamma radiation level, the light
detector disposed with respect to the scintillation material to
receive and convert the photons into signal data representative of
the frequency level over time of gamma radiation received, the
signal amplifier adapted to amplify the signal data, the
measurement sensor having at least one sensor output for such
amplified signal data; at least one computer processor having a
non-transient memory and a clock, the computer processor in
operable communication with the measurement sensor; wherein the
memory includes control computer program code executable by the at
least one computer processor, the control computer program code
including a first module for measurement, a second module for data
management; wherein the first module is adapted to receive the
signal data in a record file format; a temperature compensator
coupled with the temperature sensor, the temperature sensor adapted
to measure an ambient temperature with the system adapted to
communicate the ambient temperature to the temperature compensator,
such that the temperature compensator is adapted to generate a
temperature correction factor based on comparison of the ambient
temperature to a reference temperature, the temperature compensator
further adapted to apply the temperature correction factor to the
signal data to produce temperature compensated signal data; wherein
the second module is adapted to receive the signal data of a record
file from the first module and to transmit the compensated signal
data to a desired storage; and wherein the computer program code
further comprises a third module adapted to receive stored data of
a record file from the second module, to apply such stored data to
calculate changes in the compensated signal data over a desired
period, to apply stored data to a predictive model to generate
predictive data values over a desired period for such record file
as a predictive outcome, and to transmit such changes to a desired
storage.
2. The ex vivo measurement sensor of claim 1, further comprising a
radiation shielding mask for gamma radiation.
3. The ex vivo measurement sensor of claim 2, wherein the shielding
mask defines an aperture in the form of a collimator for gamma
radiation incident into the scintillation material.
4. The ex vivo measurement sensor of claim 2, further comprising an
alignment feature for removable alignment of the measurement sensor
with respect to the subject.
5. The ex vivo measurement sensor of claim 4, wherein the alignment
feature comprises a light emitter disposed within the sensor so as
permit alignment of the collimator aperture to a desired portion of
the subject by illumination of the subject.
6. The ex vivo measurement sensor of claim 5, wherein the light
emitter is a light emitting diode disposed within the aperture, the
ex vivo measurement sensor further comprising light proof sealant
about the light emitting diode to prevent the output of the diode
or ambient light to strike the scintillation material, while
permitting the scintillation material to receive incident gamma
radiation.
7. The system of claim 1, wherein the ex vivo measurement sensor
further comprises a radiation shielding mask for gamma radiation,
the shielding mask defining an aperture in the form of a collimator
for gamma radiation incident into the scintillation material; and
the system further comprising a stand alignment feature for the
removable mounting of the ex vivo measurement sensor in a
configuration relative to the subject so as to permit alignment of
the collimator aperture to a desired portion of the subject.
8. The system of claim 1, further comprising a filter for filtering
the amplified signal data based on amplitude.
9. The system of claim. 8, wherein the filter comprises a voltage
comparator.
10. The system of claim 8, wherein the filter further comprises an
analog to digital converter and control computer program code
adapted to compare digital amplified signal data to a reference
level.
11. A device for the detection of radiation, the device comprising:
a measurement sensor having a housing, a scintillation material, a
light detector, a light shield, a temperature sensor, a signal
amplifier, a sensor processor, a nontransient sensor memory, and a
sensor power supply, the light detector, signal amplifier, sensor
processor, sensor memory, and sensor power supply in operable
communication by a printed circuit board assembly, the printed
circuit board assembly having a board defining a plane having a
first surface and an opposing second surface, the light shield
adapted for mounting onto the first surface of the board and
shielding the scintillation material and light detector from
ambient light; wherein the scintillation material has first width
parallel with the plane and the light detector has a second width
parallel with the plane; the light shield defines a first cavity
with a third width equal or greater than the first width such that
the first cavity is adapted to receive the scintillation material
and the light shield defines a second cavity with a fourth width
equal or greater than the second width such that the second cavity
is adapted to receive the light detector; and the scintillation
material and light detector disposed within the light shield with
the scintillation material adapted to receive a level of gamma
radiation and to emit photons representative of the gamma radiation
level, the light detector disposed with respect to the
scintillation material so as to be adapted to receive and convert
the multiplied photons into signal data representative of the level
of radiation received, wherein the first and second cavities are in
communication and in such proximal relation that the light shield
optically aligns the scintillation material to the light detector
when the scintillation material is received by the first cavity and
the light detector is received by the second cavity, and operably
engaged with the printed circuit board assembly; and the signal
amplifier adapted to amplify the signal data, the sensor memory
including a measurement sensor identifier, the measurement sensor
having at least one sensor output port for such amplified signal
data.
12. The device of claim 11, wherein the light shield is mounted to
the first surface of the board with solder; and wherein the light
shield is selected from a group consisting of metal: copper, brass,
bronze, steel, aluminum, nickel-silver, beryllium copper, silver,
gold, and nickel.
13. A system for the ex vivo real-time detection of gamma radiation
emitted at an area of interest by a subject from administration and
uptake over a period of time of a radioactive analyte that decays
in vivo by positron emission, the system comprising: a primary ex
vivo measurement sensor having a sensor housing with a radiation
shield, the sensor housing with the radiation shield defining a
cavity, the radiation shield further defining an aperture into the
cavity, a collimator disposed within the aperture so as to admit a
collimated gamma radiation into the cavity from the area of
interest, a scintillation material disposed within the cavity such
that the collimated gamma radiation is incident on the
scintillation material, a light detector disposed within the sensor
housing to detect light emitted from the scintillation material, a
temperature sensor, a signal amplifier, and a sensor power source,
the light detector, temperature sensor, signal amplifier, and
sensor power source in operable communication, the scintillation
material and light detector disposed within the sensor housing with
the scintillation material adapted to receive a level of gamma
radiation over the period of time from the in vivo radioactive
analyte and to emit photons representative of the gamma radiation
level, the light detector disposed with respect to the
scintillation material so as to receive and convert the multiplied
photons into signal data representative of the frequency level over
time of gamma radiation received, the signal amplifier adapted to
amplify the signal data, the measurement sensor having at least one
sensor output for such amplified signal data; a secondary ex vivo
measurement sensor that is unshielded for measuring background
gamma radiation; a collimator alignment system in operable
engagement with the sensor housing for aligning the collimator to
the area of interest; at least one computer processor having a
non-transient memory and a clock, the computer processor in
operable communication with the primary and secondary measurement
sensors; wherein the memory includes control computer program code
executable by the at least one computer processor, the control
computer program code including a first module for measurement, a
second module for data management; wherein the first module is
adapted to receive the signal data in a record file format; a
temperature compensator coupled with the temperature sensor, the
temperature sensor adapted to measure an ambient temperature with
the system adapted to communicate the ambient temperature to the
temperature compensator, such that the temperature compensator
generates a temperature correction factor based on comparison of
the ambient temperature to a reference temperature, the temperature
compensator further adapted to apply the temperature correction
factor to the signal data to produce temperature compensated signal
data; wherein the second module is adapted to receive the signal
data of a record file front the first module and to transmit the
compensated signal data to a desired storage; and wherein the
computer program code further comprises third and fourth modules,
the third module adapted to receive stored data of a record file
from the second module, (i) to apply such stored data to a
predictive model to generate predictive data values over a desired
period for such record file as a predictive outcome, and to
transmit such predictive outcome to a desired storage; and (ii) to
apply such stored data to calculate changes in the compensated
signal data over a desired period, and to transmit such changes to
a desired storage and the fourth module adapted to subtract signal
data from the secondary ex vivo measurement sensor from signal data
from the primary ex vivo measurement sensor.
14. The system of claim 13, wherein the primary ex vivo measurement
sensor further comprises a radiation shielding mask for gamma
radiation.
15. The system of claim 14, wherein the primary ex vivo measurement
sensor shielding mask defines an aperture in the form of a
collimator for gamma radiation incident into the scintillation
material.
16. The system of claim 14, wherein the primary ex vivo measurement
sensor further comprises an alignment feature for removable
alignment of the primary ex vivo measurement sensor with respect to
the subject.
17. The system of claim 16, wherein the primary ex vivo measurement
sensor alignment feature comprises a light emitter disposed within
the sensor so as permit alignment of the collimator aperture to a
desired portion of the subject by illumination of the subject.
18. The system of claim 17, wherein the primary ex vivo measurement
sensor light emitter is a light emitting diode disposed within the
aperture, the ex vivo measurement sensor further comprising light
proof sealant about the light emitting diode to prevent the output
of the diode or ambient tight to strike the scintillation material,
while permitting the scintillation material to receive incident
gamma radiation.
19. The system of claim 13, wherein the primary ex vivo measurement
sensor further comprises a radiation shielding mask for gamma
radiation, the shielding mask defining an aperture in the form of a
collimator for gamma radiation incident into the scintillation
material; and the system further comprising a stand alignment
feature for the removable mounting of the ex vivo measurement
sensor in a configuration relative to the subject so as to permit
alignment of the collimator aperture to a desired portion of the
subject.
20. The system of claim 16, further comprising a filter for
filtering the amplified signal data based on amplitude.
21. The system of claim 20, wherein the filter comprises a voltage
comparator.
22. The system of claim 20, wherein the filter further comprises an
analog to digital converter and control computer program code
adapted to compare digital amplified signal data to a reference
level.
23. A system for the ex vivo real-time detection over a period of
time of gamma radiation emitted by a subject from the
administration of a radioactive analyte that decays in vivo, the
system comprising: at least one ex vivo gamma radiation measurement
sensor to detect gamma radiation over a desired period of time and
to produce signal data associated with the desired period of time,
the ex vivo measurement sensor adapted to sensing gamma radiation
proximate to a point of administration on the subject of the
radioactive analyte; a signal amplifier in operable communication
with the gamma radiation sensor, the signal amplifier adapted to
amplify the signal data, the measurement sensor having at least one
sensor output for such amplified signal data; at least one computer
processor and a non-transient memory, the computer processor in
operable communication with the non-transient memory and the
measurement sensor output port; wherein the non-transient memory
includes computer program code executable by the at least one
computer processor, the computer program code configured for
performing the steps of receiving the amplified signal data with
the desired period of time, accessing reference data distributed
over a reference period of time, comparing the amplified signal
data to the reference data using a parametric model to determine
the probability of a proper administration of the radioactive
analyte to the subject.
24. The system of claim 23, wherein the computer program code is
further adapted to normalize the amplified signal data, and the
parametric model is a time series function of one or more of the
amplitude and slope of the amplified signal data.
25. The system of claim 24, wherein the normalization is with
respect to a maximum value of the amplified signal data over the
period of time.
26. The system of claim 24, wherein the parametric model includes
an integration of the amplified signal data over at least a portion
of the period of time.
27. The system of claim 24, wherein the parametric model includes
comparing the amplified signal data to a specified threshold value
of the reference data corresponding to infiltration of the
radioactive analyte.
28. The system of claims 23, wherein the at least one ex vivo gamma
radiation measurement sensor comprises a sensor housing, a
scintillation material, a light detector, a signal amplifier, and a
sensor power source, the light detector, signal amplifier, and
sensor power source are in operable communication, and the
scintillation material and light detector are disposed within the
sensor housing in a light proof manner, with the scintillation
material adapted to receive a level of gamma radiation over the
period of time from the in vivo radioactive analyte and to emit
photons representative of the gamma radiation level, the light
detector disposed with respect to the scintillation material to
receive and convert the photons into signal data representative of
the frequency level over time of gamma radiation received.
29. The system of claim 28, wherein the computer program code is
further adapted to normalize the amplified signal data, and the
parametric model is a time series function of one or more of the
amplitude and slope of the amplified signal data.
30. The system of claim 29, further comprising an arm-band for
removable affixation of the ex vivo measurement sensor to an arm of
the subject.
31. The system of claim 29, further comprising an alarm to announce
the determination of an improper administration.
32. A method for the ex vivo real-time detection over a period of
time of gamma radiation emitted by a subject from the
administration of a radioactive analyte that decays in vivo, the
method comprising: (i) applying at least one ex vivo gamma
radiation measurement sensor proximate to a point of administration
on the subject of the radioactive analyte; (ii) detecting gamma
radiation over a desired period of time and producing signal data
associated with the desired period of time; (iii) amplifying the
signal data using a signal amplifier in operable communication with
the gamma radiation sensor, wherein the measurement sensor having
at least one sensor output for such amplified signal data and
outputting the amplified signal data; (iv) processing the amplified
signal data using a computer processor in operative communication
with a non-transient memory and the measurement sensor output by
performing the steps of: (a) receiving the amplified signal data
associated with the desired period of time; (b) from the
non-transient memory, accessing reference data distributed over a
reference period of time; and (c) determining if the administration
of the radioactive analyte properly administered the radioactive
analyte into the subject by comparing the amplified signal data to
the reference data using a parametric model.
33. The method of claim 32, wherein the processing of the amplified
signal data further comprises the step of normalizing the amplified
signal data, and wherein the parametric model is a time series
function of one or more of the amplitude and slope of the amplified
signal data.
34. The method of claim 33, wherein the normalizing is with respect
to a maximum value of the amplified signal data over the period of
time.
35. The method of claim 33, wherein the parametric model includes
an integration of the amplified signal data over at least a portion
of the period of time.
36. The method of claim 33, wherein the parametric model includes
comparing the amplified signal data to a specified threshold value
of the reference data corresponding to infiltration of the
radioactive analyte.
Description
RELATED APPLICATIONS
[0001] The present application is a continuation-in-part of U.S.
application Ser. No. 13/840,925 filed on Mar. 15, 2013, which
claims the benefit of priority to U.S. Provisional Application No.
61/653,014, filed on May 30, 2012, both of which are hereby
incorporated in their entirety.
STATEMENT REGARDING GOVERNMENT SUPPORT
[0002] None.
FIELD OF THE INVENTION
[0003] The present invention relates to measurement and prediction
of biological processes, and more particularly to a system and
method for using localized radio-labeled tracer temporal uptake to
measure and predict biological processes, and ensuring the proper
injection or administration of radio-labeled tracer.
BACKGROUND
[0004] Oncologists are interested in knowing if the prescribed
cancer therapy is having the intended effect, in order to improve
outcomes, minimize side effects, and avoid unnecessary expenses.
Cytotoxic treatments kill tumor cells. Cytostatic treatments
inhibit cell growth leaving tumors the same size, but preventing
the spread of the disease, Cytostatic treatments inhibit cell
growth leaving tumors the same size, but preventing the spread of
the disease. Immunotherapy treatments use the body's immune system
to attack the cancer and initially result in an inflammatory
response in the tumor area before there is evidence that the body
is effectively attacking the tumor. Historically, measuring the
tumor has been the primary way for oncologists to assess treatment
effectiveness; however, we now understand that the size of the
tumor is often not the best or earliest indicator of the therapy
effectiveness. With cytotoxic treatment the tumor size reduction
only occurs after cancer cells die and the body's natural processes
eliminate dead cells; this process can often take weeks. With
cytostatic treatment, cancer cells stop growing leaving the
clinician unsure of the state of the underlying cancer. With
immunotherapy, the body's inflammatory response often masks the
tumor from proper evaluation.
[0005] The tools available to oncologists and researchers today to
assess tumor response to treatments are not ideal. Palpating the
tumor is easy and inexpensive, but it is limited to tumors close to
the surface, relies on a physician's memory and notes, and
primarily measures size. The lack of reproducibility of this
palpating process, coupled with historical reasons, contributed to
the initial acceptance of significant changes in tumor size as an
indicator of therapy assessment. Wolfgang A. Weber, et al., "Use of
PET for Monitoring Cancer Therapy and for Predicting Outcome," 46
J. Nucl. Med. (No. 6) 983.995 (June 2005). Imaging tools (CT, MRI,
x-ray) provide more precise measurements for tumors both close to
the surface and in deep tissue, but again primarily measure size,
not the ideal indicator. Molecular imaging (PET/CT scan) captures
the positron emissions from injected radio-labeled tracers captured
by live cancer cells and is routinely used for pre-therapy staging
of cancer. Visually identifying metastatic disease is the primary
means of staging cancer; however, a semi-quantitative PET/CT
measurement known as Standardized Uptake Value (SUV) is also being
used to stage cancer. For example, SUVs are used to help determine
whether or not lung nodules are malignant. SUVs are basically a
ratio of the amount of radio-labeled tracer in an area of interest
(tumor) compared to the level in the rest of the body. While
molecular imaging is a primary tool for the pre-therapy need to
stage a patient's cancer, it is also rapidly becoming the most
advanced tool for oncologists and researchers to assess tumor
response, since molecular imaging can capture the metabolic or
proliferative condition of the cancer and the size of the tumor.
Using an SUV taken from the PET images acquired approximately
60-minutes after injection or administration of a radio-labeled
tracer in the staging scans and then comparing this value to an SUV
from a follow-up PET/CT is currently the best available indicator
for therapy effectiveness.
[0006] Despite the increasing trend to use comparative PET/CT scans
in assessing tumor response in more and more cancer types as
clinical evidence continues to grow, there are still limitations
with this state of the art assessment tool. PET/CT scans are
expensive and their use is often challenged. Additionally, there
are several issues with SUV calculations. According to Dr.
Dominique Delbeke: "[t]be reproducibility of SUV measurements
depends on the reproducibility of clinical protocols, for example,
dose infiltration, time of imaging after 18F-FDG administration,
type of reconstruction algorithms, type of attenuation maps, size
of the region of interest, changes in uptake by organs other than
the tumor, and methods of analysis (e.g., maximum and mean)."
Dominique Delbeke, et al., "Procedure Guideline for Tumor Imaging
with 18F-FDG PET/CT 1.0," 47 J. Nucl. Med. (No. 5) 885-895 (May
2006). Infiltrated injection (extravasation) of radio-labeled
tracer is a complication that often goes unnoticed by clinicians.
Medhat Osman, "FDG Dose Extravasations in PET/CT: Frequency and
Impact on SUV Measurements," Frontiers in Oncology (Vol. 1:41) 1
(2011). An infiltration is a common problem that can occur when the
radio labeled tracer infuses the tissue near the venipuncture site,
and can result from the tip of the catheter slipping out of the
vein or passing through the vein. Additionally, the blood vessel
wall can allow part of the tracer to infuse the surrounding tissue.
As a result, the radio-labeled dose being delivered is inaccurate
and thus so are the SUV calculations, which can severely impact
patient treatment and research conclusions. These infiltrations may
in fact contribute to the wide variability in researcher's efforts
to characterize SUV thresholds for clinical decision making. In one
study, it was determined that the "thresholds for metabolic
response in the multicenter multiobserver non-QA settings were -34%
and 52% and in the range of -26% to 39% with centralized QA". Linda
M. Velasquez, et al., "Repeatability of 18F-FDG PET in a
Multicenter Phase I Study of Patients with Advanced
Gastrointestinal Malignancies," 50 J. Nucl. Med. (No. 10) 1646-1654
(October 2009). In local practices and even in practices and
research centers employing Quality Assurance checks, these issues
with SUV calculations have left oncologists and researchers needing
to see significant changes in SUV values to be somewhat assured
they are making sound treatment decisions or reaching proper
research conclusions.
[0007] While using SUVs comparisons from PET/CT static images are
currently the most advanced way in clinical practices to assess
tumor response to treatment, the use of dynamic images (PET images
taken at various times during the uptake of the radio-labeled
tracers) has provided researchers with kinetic information
regarding the uptake of radio-labeled tracers. In the academic
community, this kinetic information is proving to be an even better
method of assessing treatment and predicting patient outcomes than
using static SUVs. (See Lisa K. Dunnwald, "PET Tumor Metabolism in
Locally Advanced Breast Cancer Patients Undergoing Neoadjuvant
Chemotherapy: Value of Static versus Kinetic Measures of
Fluorodeoxyglucose Uptake," Clin. Cancer Res. 2011;17:2400-2409
(published online first Mar. 1, 2011)). Unfortunately, this dynamic
PET approach takes approximately three times as long as a static
PET/CT scan and thus would require several more PET scanners at
each hospital; it is clinically and economically impractical for
widespread adoption and clinical use. So while there have been
great improvements in the past few decades regarding cancer
treatment options, today's oncologists and researchers continue to
lack a timely, cost-effective, and fast way to evaluate the
effectiveness of the treatments they deliver or the research they
are conducting.
[0008] In light of the problems associated with current tumor
measurement and prediction systems, it is an object of the present
invention to provide a way to identify improperly administered
radio-labeled tracer injections (infiltrations or extravasation),
which negatively impact tumor uptake and PET results, and an
easier, less costly, and more efficient system and method for
measuring and predicting the status and/or changes in biological
processes.
SUMMARY
[0009] Disclosed are systems for identifying improperly
administered radio-labeled tracer injections and for measuring
radio-labeled tracer uptake into a biological system in an easy,
quick and relatively inexpensive manner along with requiring less
radio-labeled tracer and inflicting less discomfort on the patient.
The system can also be used to measure biological processes in
laboratory animals with higher through put and less expense than
can be accomplished today. Physicians and researchers are better
able to make proper treatment and research decisions in a cost
effective and efficient manner. Although embodiments of the system
of the present invention described below relate to quality control
checks for identifying improperly administered radio-labeled tracer
injections and measuring and predicting changes in a tumor, for
example, embodiments of the system of the present invention can be
used to measure processes in nearly any biological system. For
example, the system can be used for non-tumor brain scans,
assessing inflammation, evaluating kidney function, etc.
[0010] Any number of embodiments of the present invention provide a
hardware and software system which provides an indication of
success in the administration of radio-labeled tracer injections
and is used to gather real-time measurements of radio-labeled
tracer uptake in a biological process, for example a tumor. Sensors
measure the localized uptake of a radio-labeled tracer which is
injected into the patient or subject. In an embodiment, for
example, sensors can be placed in the following locations: (a)
directly over the tumor; (b) on the upper right arm, approximately
10 cm above the antecubital fossa; (c) on the upper left arm,
approximately 10 cm above the antecubital fossa; and (d) over
another area of interest. By placing a sensor on the upper arm,
above the injection site of the radiotracer, the device can assess
whether or not a relatively common complication in radiotracer
injection has occurred. Properly administered injections of
radio-labeled radiotracers pass underneath the injection arm sensor
within several seconds of the injection; infiltrations or
extravasations remain in the arm tissue outside the vascular system
and are detected by the arm sensor.
[0011] In any number of embodiments, measurements taken at the
sensors can be performed quickly and repeated often. The system of
the present invention reduces the amount of expensive radioactive
tracer necessary for accurate measurement readings verse the amount
required for other measurement methods and eliminates the necessity
of using a large PET scanner or similar piece of equipment for
follow-up scans (PET/CT scanners may continue to be used to stage
diagnosed cancers and to check the subject for metastasis).
Measurements made by the present approach reveal the kinetics of
the tumor, Biological differences in tumors cause different amounts
of radioactive analyte to be consumed locally as compared to normal
tissue. The present invention senses and quantifies this
consumption, then processes the data into an easy-to-read graph for
the oncologist within minutes. Comparing graphs over time--baseline
versus subsequent scans--shows the changes in tumor parameters.
Changes in biological parameters within the tumor can give the
physician insight into whether treatment is working or not.
Additionally, the present invention can use predictive algorithms
to predict likely changes in biological parameters based on one
measurement scan, which speeds the time required to know the likely
effectiveness of treatment.
[0012] In any number of embodiments, the system can comprise: (i)
one or more Measurement Sensors; (ii) a Measurement Control Device;
(iii) Computer Software capable of executing measurement and
prediction data; and (iv) Database Server Control Software.
[0013] In one embodiment, a Measurement Sensor can be a device
comprising a scintillation material; a light detector; and an
embedded processor with associated embedded software, memory, logic
and other circuitry on a printed circuit board. In an embodiment,
for example, the sensor's electronics are enclosed in a light-proof
enclosure and there can be a multi-conductor cable to enable data
communications. Mechanical design of the housing can be used to
accurately control the placement of the scintillation material.
[0014] In one embodiment, a measurement control device can be, for
example, a device comprising a display screen, a keypad and data
communications connectors. The control device can further comprise
an embedded processor with associated embedded software, memory, a
real-time clock, and other associated logic and circuitry on a
printed circuit board. In an embodiment, there can be multiple data
communications connectors to enable the attachment of multiple
measurement sensors. Another embodiment of the control device also
includes a data communications connector to enable connection to a
computer.
[0015] In any number of embodiments, the specialized computer
software used in the system of the present invention is capable of:
(1) performing diagnostic tests on the measurement control device;
(2) transferring measurement data from the measurement control
device and saving it to a record file; (3) gathering ancillary test
data from the user or other sources (radiation dose administered,
patient weight, patient blood-glucose readings, PET scan data,
etc.) and including it in the data record file; and (4)
transferring the data record file to the database server control
software.
[0016] In any number of embodiments, the database server control
software can be capable of accepting incoming data record files
from the computer software and applying one or more Algorithms to
the data received. Simple algorithms include, but are not limited
to smoothing and/or noise reduction, radioactive decay correction,
amplitude correction based on control signals, etc. More complex
algorithms can be machine learning algorithms such as
Classification Decision Trees, Rule Learning, Inductive Logic,
Bayesian Networks, etc. Measurement data can be stored in a central
database while the Algorithm output can be used to generate reports
for the user. These reports can indicate estimated parameters or
even estimated future parameters of a tumor or other biological
process.
[0017] Some system embodiments may be directed to the ex vivo
real-time detection of gamma radiation emitted by a subject from
administration and uptake over a period of time of a radioactive
analyte that decays in vivo by positron emission. These systems may
include at least one ex vivo measurement sensor, at least one
computer processor having a non-transient memory and a clock, the
computer processor in operable communication with the measurement
sensor, a temperature compensator, and computer program code, An ex
vivo measurement sensor may have a sensor housing, a scintillation
material, a light detector, a temperature sensor, a signal
amplifier, and a sensor power source. The light detector,
temperature sensor, signal amplifier, and sensor power source may
generally be in operable communication. The scintillation material
and light detector may be disposed within the sensor housing in a
light proof manner, with the scintillation material adapted to
receive a level of gamma radiation over the period of time from the
in vivo radioactive analyte and to emit photons representative of
the gamma radiation level. The light detector may be disposed with
respect to the scintillation material so as to receive and convert
the photons into signal data representative of the frequency level
over time of gamma radiation received. The signal amplifier may be
adapted to amplify the signal data, the measurement sensor having
at least one sensor output for such amplified signal data.
[0018] The at least one computer processor may include a
non-transient memory and a clock, with the computer processor being
in operable communication with the measurement sensor. The memory
may have control computer program code executable by the at least
one computer processor. The control computer program code may
include a number of software modules, such as a first module for
measurement, a second module for data management (with "module"
intended to simply mean portion of software program code directed
to the function).
[0019] A temperature compensator may be coupled with the
temperature sensor, such that the temperature sensor is adapted to
measure an ambient temperature. The system may thus communicate the
ambient temperature to the temperature compensator, so that the
temperature compensator generates a temperature correction factor
based on comparison of the ambient temperature to a reference
temperature. The temperature compensator may be further adapted to
apply the temperature correction factor to the signal data to
produce temperature compensated signal data.
[0020] The first module may be adapted to receive the signal data
in a record file format, and the second module may be adapted to
receive the signal data of a record file from the first module and
to transmit the compensated signal data to a desired storage. The
computer program code may further include a third module adapted to
receive stored data of a record file from the second module, and to
apply such stored data to calculate changes in the compensated
signal data over a desired period. This module may also apply
stored data to a predictive model to generate predictive data
values over a desired period for such record file as a predictive
outcome, and to transmit such changes to a desired storage.
[0021] Optionally, the ex vivo measurement sensor may include a
radiation shielding mask for gamma radiation. The shielding mask
may define an aperture in the form of a collimator for gamma
radiation incident into the scintillation material. An alignment
feature or device may be included for removable alignment of the
measurement sensor with respect to the subject, in some cases, the
alignment feature may include a light emitter disposed within the
sensor so as permit alignment of the collimator aperture to a
desired portion of the subject by illumination of the subject.
Optionally, the light emitter may be a light emitting diode (LED)
disposed within the aperture, and optionally the ex vivo
measurement sensor may further include light proof sealant about
the LED to prevent the light from the output of the diode for
ambient light) to strike the scintillation material, while
permitting the scintillation material to receive incident gamma
radiation.
[0022] Optionally, the ex vivo measurement sensor may further
include a radiation shielding mask for gamma radiation, with the
shielding mask defining an aperture in the form of a collimator for
gamma radiation incident into the scintillation material; and the
system further may include a stand alignment device or feature for
the removable mounting of the ex vivo measurement sensor in a
configuration relative to the subject so as to permit alignment of
the collimator aperture to a desired portion of the subject.
[0023] Optionally, the third module may detect infiltration
conditions, in one approach, the third module may calculate changes
in the compensated signal data in order to determine infiltration
of radioactive analyte, in another approach, the predictive model
may include data representative of radiation frequency over time
associated with infiltration of the analyte within the subject for
determining an infiltration. Such a predictive model may include
data representative of spike of radiation frequency over time
associated with administration of the analyte for determining
proper administration of the analyte. An alarm or indicator may be
included to announce the determination of infiltration. Also
optionally, some embodiments may include an arm-band for removable
affixation of the ex vivo measurement sensor to an arm of the
subject.
[0024] Optionally, a noise reduction filter may be included for
filtering the amplified signal data based on amplitude or pulse
height. Such a filter may be implemented with a voltage comparator.
Alternatively, the filter may comprises an analog to digital
converter and control computer program code adapted to compare
digital amplified signal data to a reference level.
[0025] A further system embodiment may also be directed to the ex
vivo real-time detection of gamma radiation emitted at an area of
interest by a subject from administration and uptake over a period
of time of a radioactive analyte that decays in vivo by positron
emission. Such an embodiment may include a primary ex vivo
measurement sensor and a secondary ex vivo measurement sensor. The
primary ex vivo measurement sensor may include a sensor housing
with a radiation shield, the sensor housing with the radiation
shield defining a cavity, the radiation shield further defining an
aperture into the cavity, a collimator disposed within the aperture
so as to admit a collimated gamma radiation into the cavity from
the area of interest, a scintillation material disposed within the
cavity such that the collimated gamma radiation is incident on the
scintillation material, a light detector disposed within the sensor
housing to detect light emitted from the scintillation material, a
temperature sensor, a signal amplifier, and a sensor power source.
The light detector, temperature sensor, signal amplifier, and
sensor power source in operable communication.
[0026] In general, the scintillation material and light detector
may be disposed within the sensor housing with the scintillation
material adapted to receive a level of gamma radiation over the
period of time from the in vivo radioactive analyte, and to emit
photons representative of the gamma radiation level. As above, the
light detector disposed with respect to the scintillation material
is adapted to receive and convert the multiplied photons into
signal data representative of the frequency level over time of
gamma radiation received. The signal amplifier may amplify the
signal data, and the measurement sensor may have at least one
sensor output or port for such amplified signal data.
[0027] In this embodiment, the secondary ex vivo measurement sensor
may be unshielded for measuring background gamma radiation. In
addition, a collimator alignment system may be provided in operable
engagement with the sensor housing for aligning the collimator to
the area of interest,
[0028] A temperature compensator may be coupled with the
temperature sensor, such that the temperature sensor is adapted to
measure an ambient temperature. The system may thus be adapted to
communicate the ambient temperature to the temperature compensator,
so that the temperature compensator generates a temperature
correction factor based on comparison of the ambient temperature to
a reference temperature. The temperature compensator may be further
adapted to apply the temperature correction factor to the signal
data to produce temperature compensated signal data.
[0029] The at least one computer processor includes a non-transient
memory and a clock, with the computer processor in operable
communication with the primary and secondary measurement sensors.
The memory may have or store control computer program code
executable by the at least one computer processor, the control
computer program code may have a first module for measurement and a
second module for data management. The first module may be adapted
to receive the signal data in a record file format. The second
module is adapted to receive the signal data of a record file from
the first module and to transmit the compensated signal data to a
desired storage. Also included may be third and fourth modules of
computer program code, the third module adapted to receive stored
data of a record file from the second module, (i) to apply such
stored data to a predictive model to generate predictive data
values over a desired period for such record file as a predictive
outcome, and to transmit such predictive outcome to a desired
storage; and (ii) to apply such stored data to calculate changes in
the compensated signal data over a desired period, and to transmit
such changes to a desired storage and the fourth module adapted to
subtract signal data from the secondary ex vivo measurement sensor
from signal data from the primary ex vivo measurement sensor.
[0030] This embodiment may include options corresponding to the
options of the foregoing embodiment, though as appropriate for the
primary ex vivo measurement sensor.
BRIEF DESCRIPTION OF THE DRAWINGS
[0031] FIG. 1 is an illustration of an overview of the system.
[0032] FIG. 2 is a schematic of a measurement sensor of an
embodiment of the system.
[0033] FIG. 3 is shows an embodiment of a measurement sensor of the
system.
[0034] FIGS. 4A-4C illustrate optional aspects of the system.
[0035] FIGS. 5A-5C illustrate embodiments of measurement control
devices.
[0036] FIG. 6 illustrates an embodiment of computer program code of
the system.
[0037] FIG. 7 shows an embodiment of a printed circuit board and
light shield.
[0038] FIGS. 8A- 8B illustrate an embodiment of a light shield.
[0039] FIG. 9 shows an aspect of embodiments of the system.
[0040] FIGS. 10A-10B show embodiments of a measurement sensor.
[0041] FIG. 11 is a diagram illustrating locations on a subject's
body where sensors may be placed.
[0042] FIG. 12 is a flow diagram of an embodiment of components the
system.
[0043] FIG. 13 is a schematic diagram illustrating aspects of an
embodiment of the system.
[0044] FIG. 14 is a schematic of an embodiment of a measurement
sensor.
[0045] FIG. 15 is a schematic diagram illustrating aspects of an
embodiment of a measurement sensor.
[0046] FIG. 16 is a detailed exploded view of an embodiment of a
measurement sensor.
[0047] FIG. 17 is a flow diagram illustrating an embodiment of
measurement sensor operation.
[0048] FIG. 18 a schematic diagram illustrating aspects of an
embodiment of a measurement control device.
[0049] FIG. 19 is a front prospective view of an embodiment of a
measurement control device.
[0050] FIG. 20 is a front prospective view of an embodiment of a
measurement control device with measurement sensors attached.
[0051] FIG. 21 is a flow diagram illustrating measurement control
device operation in an embodiment.
[0052] FIG. 22 is a flow diagram illustrating computer software
operation in an embodiment.
[0053] FIG. 23 is a flow diagram illustrating database controller
software operation in an embodiment of the system.
[0054] FIG. 24-26 show the output from an injection arm sensor from
administration or injection of a radioactive analyte, with FIG. 24
a proper administration and FIGS. 25 & 26 showing improperly
administered radioactive analyte.
[0055] FIGS. 27 and 28 shows an embodiment of a combined
measurement sensor and measurement controller, along with an
embodiment of an arm band.
[0056] FIG. 29 shows an embodiment of a light shield.
[0057] FIG. 30 shows an exploded view of an embodiment of a light
shield and the internal components that are being shielded from
light.
[0058] FIG. 31 shows an embodiment of a light shield combined with
an alignment light source.
[0059] FIG. 32 shows a cut-away view of an embodiment of a light
shield combined with an alignment light source.
[0060] FIG. 33 shows an exploded view of an embodiment of a light
shield combined with an alignment light source.
[0061] FIG. 34 shows an embodiment of a measurement controller.
[0062] FIG. 35 shows an embodiment of two daisy chained measurement
controllers.
[0063] FIGS. 36 and 37 show embodiments of a measurement
sensor.
[0064] FIG. 38 shows an exploded view of an embodiment of a light
shield on an embodiment of a measurement sensor.
[0065] FIGS. 39 and 40 show a view of an embodiment of a radiation
shielding mask alignment device.
[0066] FIG. 41 shows an embodiment of a radiation shielding mask,
while FIG. 42 shows a top view of an embodiment of a radiation
shielding mask collimator.
[0067] FIG. 43 shows a bottom view of an embodiment of a radiation
shielding mask and collimator.
[0068] FIG. 44 shows an embodiment of a measurement sensor attached
to an embodiment of a radiation shield.
[0069] FIG. 45 shows an embodiment of a radiation shield alignment
device and an embodiment of a radiation shield.
[0070] FIG. 46 shows a cut away view of an embodiment of a
measurement sensor attached to an embodiment of a radiation
shield.
[0071] FIG. 47 shows a cut away view of an embodiment of a
measurement sensor attached to an embodiment of a radiation
shield.
[0072] FIG. 48 shows a cut away view of an embodiment of a
radiation shield alignment device attached to an embodiment of a
radiation shield.
[0073] FIG. 49 shows an embodiment of a measurement sensor and
attached radiation shield attached to a measurement sensor
stand.
[0074] FIG. 50 shows a detailed view of an embodiment of a
measurement sensor
[0075] FIG. 51 shows an embodiment of a measurement sensor attached
to an embodiment of a radiation shielding mask with adjustment
legs.
[0076] FIG. 52 shows an embodiment of a measurement sensor attached
to an embodiment of a radiation shielding mask with adjustment
legs.
[0077] FIGS. 53 and 54 show embodiments of measurement sensors
daisy chained together.
[0078] FIG. 55 shows three embodiments of measurement sensors.
[0079] FIG. 56 shows an embodiment of a measurement sensor with
attached external push button.
[0080] FIG. 57 shows a cut away view of an embodiment of a
measurement sensor with backscatter material.
[0081] FIG. 58 shows an embodiment of a measurement sensor housing
with integrated locating structure for a backscatter material.
[0082] FIG. 59 is a method implementation of the present
approach.
DETAILED DESCRIPTION
[0083] Disclosed is a system for measuring gamma radiation emitted
from an in-vivo administered radioactive analyte. If repeated
measurements are made, these measurements will show changes in the
measured radiation over time. These repeated measurements can be
used to calculate parameters related to the data. The repeated
measurements can also be used as inputs to predictive algorithms to
predict future parameters.
[0084] The system is a hardware and software system which can be
used to gather real-time or dynamic measurements of radio-labeled
tracer uptake in a biological process, for example a tumor, muscle,
or other tissue. It employs a sensor for the detection of gamma
radiation emitted by a subject from a systemic or local
administration of a radioactive analyte that generally decays in
vivo by positron emission. A sensor for gamma ray detection enables
the use of ex vivo or in-vivo devices, while ex-vivo devices can be
safer for the subject due to their less intrusive design. Elements
and capabilities of embodiments of the system are described in more
detail below.
[0085] The system 10 employs a scintillation material 20 that
converts gamma radiation to visible light. A light detector 21 then
converts the visible light to an electrical signal. This signal is
amplified and is processed to measure the captured radiation. In ex
vivo embodiments, temperature of the sensor is recorded along with
this radiation measurement, and this data may be collected by a
measurement controller or control device 12 into a record file 80.
This record file 80, along with others like it from previous
measurement sessions, may be used as inputs to calculate data
parameters or as input to predictive models to predict data
parameters. Record file 80 is intended simply to denote a
collection of data by subject 5, and such other criteria applicable
to the circumstances, such as tumor location, condition, time of
test, etc,
[0086] An embodiment of system 10 shown in FIG. 1 is directed to
the detection of gamma radiation emitted by a subject 5 (not shown)
from systemic administration of a radioactive analyte that decays
in vivo by positron emission. The system 10 may include one or more
measurement sensors 11 (or device for the detection of radiation),
a measurement control device 12, an optional processing station 70,
and optional database 75. Communication links 7 may be wired or
wireless, depending on the application, and may extend data
reporting or other communication to networks or the internet 77.
The system 10 may include a visible, audible, or other means of
indicating the status of the radioactive analyte injection,
including the likelihood of injection infiltration.
[0087] With reference to FIG. 2, measurement sensor 11 may have a
sensor housing 25 (not shown), a scintillation material 20, a light
detector 21, a temperature sensor 36, a signal amplifier 33, a
sensor processor 22, a non-transient sensor memory 30, and a sensor
power supply 32. Light detector 21, temperature sensor 36, signal
amplifier 33, sensor processor 22, sensor memory 30, and sensor
power supply 32 may be in operable communication, whether by
wiring, circuit board tracing, etc.
[0088] As shown in the exploded illustration of FIG. 3,
scintillation material 20 and light detector 21 may be disposed or
located within housing 25 for use, depending on the application.
Sensor housing 25 may be fabricated of metal (e.g., nickel, copper,
brass, bronze, steel, aluminum, nickel-silver, beryllium-copper,
etc.) or plastic (PE, PP, PS, PVC, ABS, etc.). Such sensor housing
25 may optionally be light proof, so as to protect scintillation
material 20 and light detector 21 from ambient or surrounding
light. Optionally, sensor housing 25 may define an outer surface
and comprises a light-proof coating on the outer surface. Sensor
housing 25 may also protect such internal components from
environmental degradation, such as the exposure of scintillation
material 20 to elevated humidity. Sensor housing 25 may include or
incorporate a shielding mask 38 or shield for the radiation of
concern, such as the ex vivo detection of gamma radiation.
Shielding mask 38 may be fabricated from materials such as iridium,
platinum, tungsten, gold, palladium, lead, silver, molybdenum,
copper, nickel, bronze, brass, iron, steel, zinc, titanium, and
aluminum. As shown in FIGS. 57 and 58, any number of embodiments
the sensor housing 25 could include a structure for placement and
alignment of a backscatter material 82.
[0089] In use, and as shown in FIGS. 4A-C, embodiments of sensor
housing 25 may include an adhesive 25A adapted for the removable
attachment of the housing to the skin of the subject 5. Optionally,
system 10 may include a measurement sensor carrier 35 adapted to
removably engage with the measurement sensor 11. The measurement
sensor carrier 35 may define a carrier surface with a portion of
which may comprise an adhesive 35A adapted for removable attachment
of the measurement sensor carrier 35 to the skin of a subject 5
(not shown). Optionally, measurement sensor carrier 35 includes or
defines one or more alignment features 35F that permit the repeated
alignment of the measurement sensor carrier 35 to the subject, For
example in the embodiment as shown, measurement sensor carrier 35
defines two features 35F that could be used to align a marker to
make a mark or stain dot on the skin of subject 5. For a repeated
trial, measurement sensor carrier 35 might be placed in a position
so that alignment features 35F might align with the marks on the
skin of subject 5, ensuring that measurement sensor 11 is in the
proper location. Measurement feature 35F may include a variety of
approaches depending on the application, such as pads for temporary
tattoo markings, peripheral outline ridges, guides permitting the
marking of orientation axes, etc. Additionally, embodiments of
sensor housing 25 may include a means of attachment to an arm band
78 for attachment to the arm of subject 5. This arm band may
include hook and loop fasteners 79 or other means of securing to
subject 5. An embodiment may include a pocket or other means of
securing the sensor 11 with respect to the arm band.
[0090] Sensor power supply 32, or the other power supplies
discussed herein, may be a battery, a hardwire power connection,
transformer, or some form or source of power generation. In some
embodiments, sensor power supply 32 in particular, may be a
microelectromechanical machine adapted to generate electricity from
subject 5, possibly employing the motion of subject 5, or blood
pressure, etc.
[0091] Scintillation material 20 may be placed within a gamma
radiation flux, with scintillation material 20 being adapted to
receive a level of gamma radiation from the in vivo radioactive
analyte and to emit photons representative of or corresponding to
the gamma radiation level. Light detector 21 may be juxtaposed,
located, or generally disposed with respect to the scintillation
material 20 so as to be adapted to receive and convert the
multiplied photons into signal data representative of the level of
gamma radiation received. It is contemplated that some applications
may include mechanisms or structure for directing light from
scintillation material 20 to light detector 21, such as fiber
optics, prisms, reflectors, etc. Optionally, and as shown in FIG.
3, light detector 21 may have an active area 21A sensitive or
receptive to light as described herein, and the scintillation
material 20 may be configured and sized to substantially match the
active area. Which may improve efficiency and reduce the effect of
stray light or background signals.
[0092] The scintillation material 20 may be selected for or adapted
to the radiation detection application. In some embodiments for
gamma radiation, scintillation material 20 may be selected from a
group consisting of bismuth germanate, gadolinium oxyorthosilicate,
cerium-doped lutetium oxyorthosilicate, cerium-doped yttrium
oxyorthosilicate, sodium iodide, thallium-doped sodium iodide,
polyvinyltoluene, and cadmium zinc telluride.
[0093] Measurement sensors 11 may include a signal amplifier 33
that is adapted to amplify the signal data, a sensor memory 30
including a measurement sensor identifier 16 (FIG. 6), and at least
one sensor output port 27 for communication or output of the
amplified signal data Depending on the mode of communication
desired, sensor output port 27 may be any of a variety of ports,
such as electrical jack, computer communication (e.g., CAT-5),
optical, infrared, radio transmitter, etc.
[0094] In reference to the examples in FIGS. 5A-C, the system 10
may include a controller or measurement control device 12 having a
control processor 42, a non-transient control memory 40, a control
power supply 52, and a clock 48, all in operable communication,
whether by wiring, circuit board tracing, etc. The measurement
control device 12 may include a control input port 47 operably
engaged with the sensor output port 27 (not shown) and adapted to
receive amplified signal data from the measurement sensor 11.
Operable engagement may include wired or wireless communication, in
any of a variety of communication protocols. For example, control
input port 47 may be operably engaged with the sensor output port
27 by cable (e.g., multiconductor cable 24), circuit board tracing,
or by wireless communication. In addition to amplified signal data,
it may be desirable to communicate other data or information from
measurement sensor 11 to measurement control device 12, such as
operating parameters, power storage, equipment status, or other
sensor data. Optionally, measurement control device 12 may include
a display 44 and data entry device 45, such as a touch screen, or
other input/output structure. Embodiments may include a controller
or measurement control device 12 and one or more sensors 11
contained within the same housing, and operably engaged.
[0095] The control memory 40 may, among other things, include
control computer program code 56 (FIG. 6) executable by the control
processor 42. Control computer program code 56, for example, may
include a first module 61 for implementing measurement functions
and a second module 62 for data management. For example, the first
module 61 may be adapted to receive a previously assigned
measurement sensor identifier 16 (discussed below), the signal
data, and a subject identifier and to associate the signal data,
sensor identifier, and measurement sensor identifier 16 in a record
file 80 format. The second module 62 may be adapted to receive the
signal data of a record file 80 from the first module 61 and to
transmit the compensated signal data to a desired storage. Such
storage may be local memory (e.g., sensor or control), external
memory, a remote computer memory, networked memory (wireless or
wired), or memory accessed via the internet.
[0096] The system 10 may include a temperature compensator 50
coupled with the temperature sensor 36, the temperature sensor 36
adapted to measure an ambient temperature within the system 10
adapted to communicate the ambient temperature to the temperature
compensator 50. In this way, the temperature compensator 50 may be
adapted to generate a temperature correction factor based on
comparison of the ambient temperature to a reference temperature.
As discussed below, components within measurement sensor 11 may be
temperature sensitive. The temperature compensator 50 may also be
adapted to apply the temperature correction factor to the signal
data to produce temperature compensated signal data. Temperature
compensation may not be required for embodiments directed to in
vivo sensing. Additionally, some embodiments of the system 10 may
include a means of temperature response calibration which would
nullify the impact of temperature on the operation of system 10.
This nullification could be accomplished by measuring the response
a sensor 11 has with respect to temperature, and then modifying the
parameters of amplifier 33 or other circuit components so as to
counteract this temperature response.
[0097] Optionally, as shown in FIGS. 7-8, and FIGS. 29-33,
embodiments of measurement sensor 11 may include an internal
disposed light shield 28. Such an embodiment may include a printed
circuit board assembly 23P having a board 23 defining a plane with
a first surface 23A and an opposing second surface 23B. Light
shield 28 may be adapted for mounting onto the first surface 23A of
the board 23, thereby shielding the scintillation material 20 and
light detector 21 from ambient light. The scintillation material 20
and light detector 21 may be ensconced in or surrounded by light
shield 28. For example, given that the scintillation material 20
has a first width parallel with the plane and the light detector 21
has a second width parallel with the plane, then light shield 28
may define a first cavity 28A with a third width equal or greater
than the first width such that the first cavity 28A is adapted to
receive the scintillation material 20, and the light shield 28 may
also define a second cavity 28B with a fourth width equal or
greater than the second width such that the second cavity 28B is
adapted to receive the light detector 21. First and second cavities
28A., 28B may be in communication and in such proximal relation
that the light shield 28 optically aligns the scintillation
material 20 to the light detector 21 when the scintillation
material 20 is received by the first cavity 28A and the light
detector 21 is received by the second cavity 28B. These components
may be operably engaged with the printed circuit board assembly 23P
when mounted. For purposes herein, the term "width" is intended to
connote an effective width that permits the nesting described, and
not any particular required cross sectional shape. In other words,
the term "width" is intended to permit the reception of the
components as described, and not to limit cross section shape of
those components beyond their interrelation. In an embodiment of
the light shield 28, a light proof sealant 81 may be used to seal
the cavities after assembly of the scintillation material 20 and
light detector 21. This light proof sealant 81 may, for example, be
an epoxy, caulk, potting compound, etc.
[0098] Such a light shield 28 may be made from materials selected
from a group of metals (e.g., copper, brass, bronze, steel,
aluminum, nickel-silver, beryllium copper, silver, gold, nickel),
or plastic (e.g., ABS, Acetal, Acrylic, Fluoroplastic,
Polycarbonate, Nylon, PVC, Polypropylene, Polystyrene, Polyethylene
ABS, Acetal, Acrylic, Fluoroplastic, Polycarbonate, Nylon, PVC,
Polypropylene, Polystyrene, Polyethylene). Optionally, the light
shield 28 may be made from one material and plated or coated in
another, to enhance its ability to be soldered or mounted on
printed circuit board assembly 23P.
[0099] If made from metal or metal clad or plated plastic, the
light shield 28 may be fixed into place on printed circuit board
assembly 23P as a surface-mount-component using either leaded or
lead-free solder, or as a through-hole-component using portions of
the light shield 28 that protruded through holes in the circuit
board, the holes then filled with solder. If made from plastic, the
light shield 28 may be fixed into place on the printed circuit
board assembly 23P as a snap-on part with portions of the shield
that protrude through holes in the printed circuit board assembly
23P that spring into position and resist reversing out of the
holes, as a swage-on part with portions of the shield that protrude
through such holes and that are then melted or swaged to prevent
them from reversing out of the holes. Additionally, light shield 28
may be mounted detached from the printed circuit board,
incorporating wired connections thereto.
[0100] Optionally, light shield 28 may have one or more
through-holes in it to allow pressure to equalize during assembly
or to allow for out-gassing during assembly. Such holes may then be
covered, possibly with light-proof foil tape or sealant 81, after
assembly to complete the light-proof nature of the shield.
[0101] As shown in FIG. 7, light shield 28 may also enclose a light
emitter 31 (e.g., LED, light bulb, laser diode) such that the light
emitter could be used to generate pulses of light within the
enclosure of the light shield 28 to test the light detector 21.
Thus, system 10 may include a light emitter 31 in operable
communication with the sensor power supply 22, the light emitter 31
disposed within first or second cavity 28A, 28B (or other proximal
cavity), such that the light shield 28 is adapted to receive the
light emitter 31 in a location that is proximal to the light
detector 21.
[0102] In some embodiments, the control computer program code 56
further comprises a third module 63 adapted to receive stored data
of a record file from the second module 62. The third module 63 may
apply such stored data to a predictive model to generate predictive
data values over a desired period for such record file as a
predictive outcome, and to transmit such predictive outcome to a
desired storage. In other embodiments, the third module 63 may to
apply such stored data to calculate changes in the compensated
signal data over a desired period, and to transmit such changes to
a desired storage. In other embodiments, the third module 63 may to
apply such stored data to calculate changes in the compensated
signal data from background data over a desired period, and to
transmit such changes to a desired storage. Such background data
may be drawn from a second measurement sensor 11, a previously
calculated background radiation level, or a separate radiation
sensor, depending on the application, in other embodiments, the
third module 63 may be adapted to apply such stored data to
calculate the quality of a radioactive analyte injection, such as
to monitor changes in compensated signal data or otherwise
calculate the likelihood of injection infiltration. A result of
this may be transmitted to a display and/or a desired storage. This
could alert or inform the user of the status, whether by visual,
audible or other indication means.
[0103] FIG. 24 shows the radiation pulse count amplitude or output
over time from an injection arm sensor 11 with a properly
administered radioactive analyte, with a low level prior to
injection 88, an injection spike 89, and a low level post injection
90. This signal data forms a distinctive parametric pattern (i.e.,
amplitude, slope, time), which is characteristic of the proper
administration of a radioactive analyte. The injection spike 89,
followed by the low level post injection demonstrates dispersal of
the radioactive analyte after a proper administration or injection.
FIG. 25 shows an output from an injection arm sensor 11 with an
improperly administered radioactive analyte (i.e., infiltration or
extravasation) in 91, as well as non-administration arm low levels
92, and illustrating the approximate extremely high level of counts
or amplitude at the approximate time 93 at which a PET Scan might
typically be taken. FIG. 26 shows an output from an injection arm
sensor 11 with another improperly administered radioactive analyte
(i.e., infiltration or extravasation) in 94, as well as
non-administration arm low levels 95, and illustrating the
approximate normal low level of counts or amplitude (obtained by
extrapolating from available measurements, as shown by the dashed
lines) at the approximate time 96 at which a PET Scan might
typically be taken, The parametric patterns and data characteristic
of improper administration can thus be distinguished in comparison
to the parametric pattern and data of proper administration.
Without the present approach, the improper administration would be
impossible for clinicians to detect. In addition to infiltration or
extravasation, improper administration may include or be
characterized by other inaccuracies in the desired dispersion of
radioactive analyte (e.g., protocol deviation).
[0104] In some embodiments, system 10 may include a processing
station 70 (FIGS. 1 & 9). Processing station 70 may be a
computer in communication with measurement control device 12.
Embodiments of processing station 70 may include a station
processor, a non-transient station memory, and a station power
supply; the station processor, station memory, and station power
supply are in operable communication. The processing station 70 may
have a station input port operably engaged with the control output
port and adapted to receive data from the measurement control
device 12. In some embodiments, the role of measurement control
device 12 and station 70 may be merged.
[0105] Similar to measurement control device 12, the processing
station 70 may include station computer program code 76 executable
by the station processor, the station computer program code
including a third module 63 adapted to receive stored data of a
record file from the second module 62, to apply such stored data to
a predictive model to generate predictive data values over a
desired period for such record file as a predictive outcome.
[0106] Optionally, processing station 70 may include a docking
device 71 for the measurement control device 12. The docking device
71 may be in operable communication with the station processor.
Docking device 71 could be adapted to receive the measurement
control device in the form of a holder, retainer, charger, or
cradle. When measurement control device 12 is docked, the docking
device 71 may provide an electrical connector that engages with
measurement control device 12 for data communication and power
exchange. In one embodiment, the third module 63 may be adapted to
calculate the quality of the radioactive analyte injection. Whether
by identifying certain changes or modelling, such as to calculate
the likelihood of injection infiltration. The station computer
program code could then transmit the result of this calculation to
a desired storage. Additionally, the station computer program code
could alert the user of the calculation result using visual,
audible or other indication means.
[0107] In some embodiments, a predictive model may be a
classification machine learning model. In other embodiments,
predictive model may be an unsupervised cluster analysis. Such an
unsupervised cluster analysis, or other predictive model, may be
adapted to predicting future outcome, predicting an effect of tumor
treatment, and predicting metastasis.
[0108] Some embodiments may involve multiple measurement sensors
11. For example, a system 10 may include a first and second
measurement sensor 11, the first measurement sensor 11 adapted to
the detection of test gamma radiation emitted by a subject from
systemic or local administration of a radioactive analyte that
decays in vivo by positron emission proximate to a test area. The
second measurement sensor 11 may be adapted to the detection of
background gamma radiation emitted by a subject from systemic or
local administration of a radioactive analyte that decays in vivo
by positron emission proximate to a background area. Depending on
the application, the control computer program code 56 or station
computer code 76 may further include a fourth module 64 adapted to
receive stored data of a record file from the second module 62
including data from the first and second measurement sensors 11 and
to subtract signal data from the second measurement sensor 11 from
signal data from the first measurement sensor 11. In other
applications, the fourth module 64 may be adapted to receive stored
data of a record file from the second module 62 including data from
the first and second measurement sensors 11, and to subtract signal
data from the second measurement sensor 11 from signal data from
the first measurement sensor 11. Such embodiments may permit the
subtraction of background radiation from sensor data. Additionally,
such embodiments may permit the estimation of the likelihood that
the system or local radioactive analyte injection resulted in
infiltration.
[0109] In some embodiments, the signal data may be a plurality of
pulses at a pulse frequency over time. The first module 61 may be
adapted to communicate a sampling frequency instruction to the
sensor processor 22, the sampling frequency instruction being a
function of the pulse frequency of the signal data. In some
embodiments, the first module 61 is adapted to communicate an
increasing sampling frequency instruction upon an increase in pulse
frequency.
[0110] An aspect of present approach is a sensor or device for the
detection of radiation, the device comprising a measurement sensor
11 with a housing 25, a scintillation material 20, a light detector
21, a light shield 28, a temperature sensor 36, a signal amplifier
33, a sensor processor 22, a non-transient sensor memory 30, and a
sensor power supply 32. Light detector 21, temperature sensor 36,
signal amplifier 33, sensor processor 22, sensor memory 30, and
sensor power supply 32 may be in operable communication by a
printed circuit board assembly 231. Printed circuit board assembly
23P may have a board 23 defining a plane having a first surface 23A
and an opposing second surface 23B. Light shield 28 may be adapted
for mounting onto the first surface 23A of the board 23, thereby
shielding the scintillation material 20 and light detector 21 from
ambient light. The scintillation material 20 and light detector 21
may be ensconced in or surrounded by light shield 28. For example,
given that the scintillation material 20 has a first width parallel
with the plane and the light detector 21 has a second width
parallel with the plane, then light shield 28 may define a first
cavity 28A with a third width equal or greater than the first width
such that the first cavity is adapted to receive the scintillation
material 20, and the light shield 28 may also define a second
cavity 28B with a fourth width equal or greater than the second
width such that the second cavity 28B is adapted to receive the
light detector 21. First and second cavities 28A, 28B may be in
communication and in such proximal relation that the light shield
28 optically aligns the scintillation material 20 to the light
detector 21 when the scintillation material 20 is received by the
first cavity 28A and the light detector 21 is received by the
second cavity 28B. These components may be operably engaged with
the printed circuit board assembly 23P when mounted,
[0111] The scintillation material 20 and light detector 21 are thus
disposed within the light shield 28 with the scintillation material
20 adapted to receive a level of gamma radiation and to emit
photons representative of the gamma radiation level. Light detector
21 is disposed with respect to the scintillation material 20 so as
to be adapted to receive and convert the multiplied photons into
signal data representative of the level of radiation received.
[0112] As above, the signal amplifier 33 may be adapted to amplify
the signal data, the sensor memory 30 including a measurement
sensor identifier, the measurement sensor 11 having at least one
sensor output port 27 for such amplified signal data. Optionally,
the light shield 28 may be mounted to the first surface 23A of the
board with solder. In some embodiments, light shield 28 is selected
from a group consisting of metal: copper, brass, bronze, steel,
aluminum, nickel-silver, beryllium copper, silver, gold, and
nickel.
[0113] An aspect of some embodiments of system 10 for the detection
of gamma radiation emitted by a subject is that at least one
measurement sensor 11 may have a hermetically sealed sensor housing
25 of biocompatible material, a scintillation material 20, a light
detector 21, a signal amplifier 33, a sensor processor 22, a
non-transient sensor memory 30, and a sensor power supply 32, as
shown in FIGS. 10A-10B. Light detector 21, signal amplifier 33,
sensor processor 22, sensor memory 30, and sensor power supply 32
may be in operable communication, whether by direct wiring, circuit
board tracing, wireless interaction, etc. Optionally, sensor
housing 25 biocompatible material may be selected from a group
consisting of glass, polyether ether ketone, and
ultra-high-molecular-weight polyethylene appropriate for the
application, such as meeting implantable standards for in vivo
applications, for example. As a further option, sensor housing 25
may comprise an anchor 25F for securing an in vivo application in a
desired location for testing or sensing.
[0114] Similar to as discussed above with reference to FIG. 3,
light detector 21 may have an active area 21A and the scintillation
material 20 may be configured to substantially match the active
area 21A. The scintillation material 20 and light detector 21 may
be disposed within the sensor housing 25 with the scintillation
material 20 adapted to receive a level of gamma radiation from the
in vivo radioactive analyte and to emit photons representative of
the gamma radiation level, the light detector 21 disposed with
respect to the scintillation material 20 so as to be adapted to
receive and convert the multiplied photons into signal data
representative of the level of gamma radiation received. The signal
amplifier 33 may be adapted to amplify the signal data. The sensor
memory 30 may include a measurement sensor identifier 16, the
measurement sensor 11 having at least one wireless sensor output
port 27 for such amplified signal data.
[0115] Such an embodiment of measurement sensor 11 may work with an
ex vivo measurement control device 12 having a control processor
42, a non-transient control memory 40, a control power supply 52,
and a clock 48. Similar to as discussed above with reference to
FIG. 5A-C, the control processor 42, control memory 40, control
power supply 52, and clock 48 may be in operable communication,
whether by direct wiring, circuit board tracing, or otherwise. The
measurement control device 12 may have a wireless control input
port 47 operably engaged with the wireless sensor output port 27
and adapted to receive amplified signal data from the measurement
sensor 11.
[0116] The control memory 40 may include control computer program
code or software 56 executable by the control processor 42 (FIG.
6). Such control computer program code or software 56 may include a
first module 61 for measurement and a second module 62 for data
management. The first module 61 may be adapted to receive the
measurement sensor identifier 16, the amplified signal data, and a
subject identifier and to associate the signal data, sensor
identifier 16, and measurement sensor identifier in a record file
80 format, The second module 62 may be adapted to receive the
amplified signal data of a record file 80 from the first module 61
and to transmit the amplified signal data to a desired storage,
[0117] Optionally, the system 10 may include an in vivo measurement
sensor 11 with a sensor housing 25 that is substantially tubular,
which defines a sensor housing outer surface 25S and a sensor
housing length 25L (FIG. 10B). In some such embodiments, the
wireless sensor output port 27 may comprise an antenna running
substantially along the length 25L of the sensor housing 25, along
with supporting transmitters, etc. Substantially along the length
simply means by general orientation or along a substantial portion,
but it need not extend for the full length or be a straight
antenna. It is contemplated, for example, that one embodiment of
sensor output port 27 may comprise a coiled antenna oriented along
a portion of length 25L, as shown in FIGS. 10A-10B. The anchor 25F
may comprise at least one raised ring about a portion of a
circumference of the sensor housing 25, which may or may not
encircle the full circumference. The at least one raised ring or
anchor 25F may disposed on the outer surface 25S and having a
height from the outer surface of about 0.1-3.0 mm to anchor sensor
housing 25 in place. Other embodiments of anchor 25F may include
features such as adhesive, raised ridges, bumps, or eyelets, to
minimize movement with respect to a patient or subject 5. Sensor
housing 25 may also be provided in other general shapes.
[0118] In such an embodiment, optionally computer program code or
software 56 (FIG. 6) may further comprise a third module 63 adapted
to receive stored data of a record file 80 from the second module
62, to apply such stored data to a predictive model to generate
predictive data values over a desired period for such record file
as a predictive outcome, and to transmit such predictive outcome to
a desired storage. In another option, control computer program code
or software 56 may comprise a third module 63 adapted to receive
stored data of a record file 80 from the second module 62, to apply
such stored data to calculate changes in the amplified signal data
over a desired period, and to transmit such changes to a desired
storage. In yet another option, control computer program code or
software 56 may comprise a third module 63 that is adapted to
receive stored data of a record file 80 from the second module 62,
to apply such stored data to calculate changes in the amplified
signal data from background radiation data over a desired period,
and to transmit such changes to a desired storage. In some
embodiments, this third module may be adapted to calculate the
quality of the radioactive analyte injection, such as to calculate
the likelihood of injection infiltration. The computer program code
could then transmit the result of this calculation to a desired
storage. Additionally, the computer program code could alert the
user of the calculation result using visual, audible or other
indication means.
[0119] In one embodiment, the signal data comprises a plurality of
pulses at a pulse frequency over time, and wherein the first module
61 is adapted to communicate a sampling frequency instruction to
the sensor processor 22, the sampling frequency instruction being a
function of the pulse frequency of the signal data. The first
module 61 may be adapted to communicate an increasing sampling
frequency instruction upon an increase in pulse frequency.
[0120] Processes that could be used in the manufacture of the
measurement sensors 11 or other components may include many that
are common within the electronics assembly industry, along with the
following specific processes. For an embodiment of the system 10
that includes a gamma radiation mask or shield 38, for example,
this mask or shield 38 may be glued, molded, swaged, screwed or
otherwise mechanically fixed into the measurement sensor housing
25. Then, the mask or shield 38 may be used as a mounting plate for
the other measurement sensor 11 components, including electrical
components and additional housing components to create a lightproof
sensor housing 25. As shown in FIGS. 57 and 58, in any number of
embodiments the sensor housing 25 could include structure for
placement and alignment of a backscatter material 82.
[0121] In another embodiment, the measurement sensor 11 components
may be arranged within the measurement sensor housing 25, and then
an epoxy, silicone or other curable fluid could be applied
surrounding the components. This method would hold the optical
components in alignment while also surrounding them with a light
proof material.
[0122] In another embodiment of the measurement sensor 11 that
includes a wireless output port 27 as an antenna, it may be
embedded in the structure of the measurement sensor housing 25. For
example, antenna wire may be arranged on a mold form, then molding
plastic may be applied around the form thus encapsulating the
wires. With this method, the antenna wires could be of numerous
designs for the optimization of antenna efficiency. Additionally,
this method could allow for a ferrite material to be placed within
the antenna portion of the housing 25 to further optimize the
antenna efficiency.
[0123] Additional aspects or optional embodiments are provided
below. The present system enables (but does not require) radiation
sensitive sensors to be placed ex vivo, such as on or near a test
subject's skin. These sensors may measure the localized uptake of a
radio-labeled tracer which is injected into the subject 5, in an
embodiment as shown in FIG. 1, measurement sensors 11 may be placed
in one or more of the following locations of FIG. 11, for example:
(a) directly over the tumor 1; (b) on the upper right arm 2,
approximately 10 cm above the antecubital fossa; (c) on the upper
left arm 3, approximately 10 cm above the antecubital fossa, and
(d) over the liver 4, immediately below the ribs and directly below
the nipple. As shown in FIG. 2, for example, an embodiment of the
system 10 may comprise: (i) one or more measurement sensors 11;
(ii) a measurement control device 12; (iii) computer software or
computer program code 13 capable of executing certain functions,
such as measurement and generation of predictive data or assessment
as to the likelihood of an injection infiltration. The system 10
may also include a desired storage for data, etc., with appropriate
databases, database management or server control software 14,
etc.
[0124] As shown in FIGS. 14 through 16, a measurement sensor 11 can
be, for example, a device comprising a scintillation material 20; a
light detector 21; and a sensor processor 22 with associated
non-transient sensor memory 30, logic or sensor software 26, and
other circuitry supporting these components in operable
communication, optionally with a printed circuit board 23P (FIG.
16). FIG. 17, for example, illustrates a flow diagram of operation
of an embodiment of an ex vivo measurement sensor 11. In operation,
a subject 5 may receive a systemic or local administration by
injection of a radioactive substance (also referred to as a
tracer). When this radioactive substance decays, it releases or
emits positrons (also referred to as high energy particles). The
measurement sensor 11 uses a scintillation material 20 to receive
gamma radiation from positron emission decay and to convert the
radiation into photons, such as pulses of light, which may then be
detected by the light detector 21. The sensor processor 22 may
enable measurement and collection of the photons, such as the
number of light pulses detected over a given amount of time. For
example, a large number of light pulses detected per unit of time
may correspond to a large concentration of radioactive material. As
the radioactive material concentration changes, the light pulses
detected per unit of time changes accordingly. By graphing the
light pulses counted versus time of data collection, a visual
representation of radioactive concentration over time may be
produced. This graph indicates how the radioactive concentration is
changing. Optionally, noise rejection 37 (FIG. 14) may comprise a
filter for filtering amplified signal data based on the height or
amplitude of such pulses. For example, noise rejection 37 may
include a voltage comparator or an analog to digital converter with
computer program code to compare the digital output to a reference
level.
[0125] Any number of small embedded processors are adequate for use
in the measurement sensor 11, and sensor processor 22 may include a
dedicated asynchronous counter of suitable size, if need for the
application and if an external one is not included in the
additional circuitry. The sensor processor 22 may be embedded in
the measurement sensor, or an external sensor processor 22 may be
provided as applicable. The sensor processor 22 may be specially
configured to satisfy various embodiments of the system 10,
depending on the requirements of the application. An FPGA or other
programmable logic device, for example, may be well suited to this
system, possibly incorporating a microprocessor sub-system within
the FPGA design.
[0126] Possible scintillation materials 20 include, but are not
limited to: Bismuth Germanate (BOO); Gadolinium Oxyorthosilicate
(GSO); Cerium-doped Lutetium Oxyorthosilicate (LSO); Cerium-doped
Lutetium Yttrium Orthosilicate (LYSO); Thallium-doped Sodium Iodide
(NaI(T1)); Plastic Scintillator (Polyvinyltoluene); or Cadmium Zinc
Telluride (CZT). In an embodiment of a measurement sensor 11,
multiple scintillation materials 20 adapted to measure different
radioisotopes may be used. In another embodiment of a measurement
sensor 11, scintillation materials 20 that do not require the use
of a light detector 21 may be used. In another embodiment of a
measurement sensor, multiple scintillation materials 20, each with
their own detection circuitry, may be included to enable a two
dimensional array of measurements.
[0127] In an embodiment of measurement sensor 11, the light
detector 21 may include a signal amplifier 33 or amplification
circuitry to handle low level signals. In another embodiment,
measurement sensor may further include a temperature sensor 36
which is coupled to a temperature compensator 50, the temperature
sensor adapted to measure an ambient or local temperature of the
scintillation material 20 and light detector 21, and to communicate
or report such temperature to temperature compensator 50.
Temperature compensator 50 being adapted to generate a temperature
correction factor based on comparison of the ambient temperature to
a reference temperature. The temperature compensator 50 may apply
the correction factor to the signal data to produce temperature
compensated signal data, or may be adapted to reporting the local
temperatures of the scintillation material 20 and light detector
21. Depending on the embodiment, in vivo detection may not require
temperature compensation in that the measurement sensor 11 might be
calibrated for normative subject temperatures. Additionally, some
embodiments of the measurement sensor 11 could include temperature
response calibration, which would nullify the impact of temperature
on system 10 operation. This nullification could be accomplished,
for example, by measuring the response a sensor 11 has with respect
to temperature, and then modifying the parameters of amplifier 33
or other circuit components so as to counteract this temperature
response.
[0128] In another embodiment of the system, a measurement sensor 11
can be, for example, a device comprising a scintillation material
20; a light detector 21 and associated signal amplifier 33 or
amplification circuitry and sensor processor 22 located on a
printed circuit board 23P in the sensor portion of the system.
Light detector 21 may be selected based on the application, such as
a photodiode or photocathode, and signal amplifier 33 (or
amplification circuitry, possibly incorporated into circuit board
23P) may include a photomultiplier or simply a signal amplifier 33.
Other associated circuitry may then then moved to the measurement
control device 12. In any number of embodiments, the measurement
sensor 11 can be provided with microelectromechanical machine
(MEMS) power generation capability such that a battery or external
power source is not necessary, A MEMs generator may be
piezoelectric based, adapted to generate electricity from a motion
of the subject 5, body heat of the subject 5, or the blood pressure
of subject 5. Alternatively, sensor power supply 32 may be a corded
power connection to either the control device. In another
embodiment, a measurement sensor 11 can be a wireless, with an
independent power supply 32.
[0129] In an embodiment of a measurement sensor 11, for example,
the electronics may be enclosed in a light-proof enclosure or
housing 25 and there can be a multi-conductor cable 24 for data
communications. Mechanical design of the housing 25 can be used to
accurately control the placement of the scintillation material 20.
As shown in FIGS. 57 and 58, in any number of embodiments, the
sensor housing 25 could include structure for placement and
alignment of backscatter material 82.
[0130] In an embodiment of a measurement sensor 11, the sensor may
include sensor housing 25 which optionally may incorporate a
shielding mask 38 for collimation of the incoming radiation for
increased directional sensitivity or a backscatter material 82 for
the reflection of incoming radiation which is not captured by the
scintillation material 20. The shielding mask 38 can be made of any
number of dense materials including, but not limited to lead,
steel, iron, aluminum, iridium, platinum, copper, cement, dense
plastic, etc. The shielding mask 38 can be tailored to protect
against specific radiation depending on the application of the
system of the present invention. As described above, sensor housing
25 may include structure for the placement and alignment of
backscatter material 82.
[0131] In an embodiment of a measurement sensor 11, for example,
the sensor could further include a removable and/or disposable
protective sleeve or case, also referred to as carrier 35. This
sleeve or carrier 35 can have adhesive (e.g., adhesive 35A) applied
in order to attach the measurement sensor 11 to a test subject 5.
This sleeve can also be used as a sanitary barrier between the
measurement sensor 11 and a test subject 5. In some embodiments,
measurement sensor 11 may further include housing 25 which itself
has adhesive used to attach the sensor 11 to a test subject 5. Some
embodiments of sensor 11 may include structure for attachment, such
as an arm band, to the arm of a subject 5. Such an arm band may
include hook and loop fasteners or other approaches of securing to
subject 5. An embodiment may include a pocket or other structure by
which sensor 11 is secured to the attachment structure or arm
band.
[0132] In any number of embodiments, measurement sensor 11 and
measurement control device 12 may include the necessary hardware
and software to enable wireless communications between them. In
such an embodiment, encryption techniques may be used to provide
security for wireless signals.
[0133] In any number of embodiments of the system of the present
invention, an individual measurement sensor can be calibrated for
radiation sensitivity. This calibration can overcome measurement
inconsistencies due to manufacturing and physical tolerances in the
sensor. Since each measurement sensor 11 has unique manufacturing
and physical tolerances and material characteristics, no two
sensors will naturally report the same measurement given the same
radiation source input. Therefore, each sensor may be exposed to a
known activity radiation source and a correction factor can then be
provided for each individual sensor. As a result, each measurement
sensor 11 used in the system 10 may be calibrated with one another
with regard to radiation sensitivity.
[0134] In any number of embodiments, an individual measurement
sensor 11 may be calibrated for temperature sensitivity. Various
components of a measurement sensor 11 are sensitive to temperature
changes and the repotted radiation activity due to temperature. It
is known that a scintillation crystal or material 20, a light
detector 21, and, to a lesser degree, amplifiers used for light
detection, for example, may be sensitive to temperature. Therefore,
a precision temperature sensor 36 may be placed locally or
proximally to the temperature sensitive elements. Ambient
temperature can then be recorded during the data collection process
so that corrections or compensation can be made to signal data or
measurement readings in order to compensate for any inaccuracies in
the measurement readings resulting from certain elements'
sensitivity to temperature, producing temperature compensated
signal data. In order to determine temperature correction factors,
a measurement sensor 11 may be subjected to a stable radiation test
source while the surrounding temperature is swept through the range
of the operating temperatures. This may be accomplished in a
laboratory temperature chamber. Through this test process,
radiation activity of a known, stable source as well as temperature
data can be recorded. A calibration curve can then be calculated
which adjusts the measured radiation activity to a normalized flat
response corresponding to expected compensated signal data,
Additionally, some embodiments of sensor 11 may include temperature
response calibration, which could nullify the effect of temperature
on system operation. Nullification may be accomplished by measuring
the response a senor 11 has with respect to temperature, and then
modifying the parameters of amplifier 33 or other circuit
components to counteract this temperature response.
[0135] In another embodiment, a measurement sensor 11 may provide
adaptive performance and measurement capabilities. For example, if
the rate of tumor growth accelerates, the sensor can automatically
respond to the change by increasing sampling frequency.
[0136] In any number of embodiments of the system, a measurement
control device 12 can be, for example, a hand-held and battery
powered device comprising a display screen, a keypad and data
communications connectors. An alternative embodiment may include
the measurement control device 12 and one or more sensors 11
contained within the same housing, and operably engaged with wires,
printed circuit board traces etc. In an alternative embodiment of
the system of the present invention, the measurement control device
12 can be a desktop-style powered device. In another embodiment,
the measurement control device 12 or other portions of system 10
may include a cradle-style charging dock for the battery operated
device. The cradle-style charging dock can charge batteries for a
hand-held device and can also initiate the capture of any
measurements in the hand-held device's memory. In another
embodiment, the measurement control device 12 may provide MEMS
power generation capability such that a battery or external power
source is not necessary.
[0137] In any number of embodiments of the system 10, as shown in
FIGS. 20 through 21 for example, a measurement control device 12
comprises a control processor 42, control software 56 (optionally
as embedded software), control memory 40, a real-time clock 48, and
other associated logic and circuitry on a printed circuit board.
The control processor 42 may be embedded in the measurement control
device 12, provided as an external processor, or optionally merged
with station 70. The control processor 42 is generally specially
configured to satisfy embodiments of the system 10. The control
device can control user-interface, data collection, and data
transmission activities. There are various microprocessors capable
of this including small embedded processors and single-board
computers. FIG. 21 is a flow diagram illustrating operation of an
embodiment of a measurement control device 12. The system 10
generally may respond to user input, keep track of sensor
attachment or association, monitor operational parameters, such as
battery level, and transfer measurement data to a desired storage,
such as an external computer. In an embodiment of a measurement
control device 12, as illustrated in FIG. 20 for example, there can
be multiple data communications connectors to enable the attachment
of multiple measurement sensors 11, as well as a data communication
to a variety of desired storage devices or networks.
[0138] In an embodiment of a measurement control device 12, the
device can further include network connectivity and control
hardware and software to incorporate the functionality of the
control computer software 56. This creates a stand-alone system at
the test site which eliminates the need for a separate computer or
computer software. Encryption and decryption methods known in the
art can be provided in any number of embodiments to secure wireless
communications.
[0139] An embodiment of a measurement control device 12 may further
include a bar code scanner for recording pertinent identification
numbers, calibration codes, etc. when printed on bar codes. An
embodiment of a measurement control device 12 can further include a
pulse-oxygen, skin resistivity, or other biological sensor in order
to incorporate additional data into the measurements collected.
Another embodiment of a measurement control device 12 can further
include a digital camera system for incorporating photos into the
data record tile. These photos could be used for sensor placement
details, for example. One embodiment of a measurement control
device 12 can further include functionality which communicates to
the user specific details pertinent to the test or test subject
being worked with. This communication can include, but is not
limited to, non-standard placement locations for the measurement
sensors 11, reminders of tumor size and location, general notes,
test related photos, etc.
[0140] In an embodiment of a measurement control device 12, for
example, a power switch can control power to all components of the
device, except possibly a real-time clock 48. The clock 48 may have
consistent hack-up power to avoid losing the programmed date and
time. When the power switch is in the "ON" configuration, power may
be applied to the device components, and a microprocessor can start
operation and test operability. The microprocessor of control
processor 42 may further test external peripherals such as the
display 44, the real-time clock 48, etc. As the tests are
performed, a display screen of the measurement control device 12
may display, for example, a waiting message. Next, at least one
measurement sensor 11 may be attached to the control device 12 via
a connector and a cable, such as multiconductor cable 24. Upon
attachment of a measurement sensor 11, the control device 12
recognizes the attachment and performs duties described below to
start up the measurement sensor 11.
[0141] In an embodiment of a measurement sensor 11, for example,
power may be supplied to the sensor via the measurement control
device 12. For example, a multi-conductor cable 24 with a connector
on the end or a plug that fits into a mating jack can be used to
connect the measurement sensor 11 to the control device 12. Power
can be supplied to the measurement sensors 11 over this cable from
the measurement control device 12. The sensors can be connected to
the measurement control device 12 before data collection and remain
connected throughout data collection. In another embodiment, the
measurement sensor 11 may include its own sensor power source 32
and non-transient sensor memory 30 to store recorded data such that
no cable might be necessary and the sensor does not need to remain
connected to the measurement control device 12 during operation. In
order to retrieve the recorded data, wireless communications may be
enabled and/or a cable may be connected to the measurement control
device 12 at a desired time.
[0142] After power is turned on to the sensor 11, as shown in FIGS.
17 and 21 for example, the sensor processor 22 may start operation
and test itself. If the self-test verifies that the measurement
sensor 11 is operational, the sensor can alert the measurement
control device 12 that the measurement sensor 11 is operational and
ready to receive an address which is an address that the control
device 12 will use to communicate with the identified measurement
sensor 11. The measurement control device 12 can next send the
measurement sensor 11 a unique address or identifier 16 assignment
(i.e., unique being sufficiently individualized for the application
to avoid confusion). After receiving the unique identifier 16
assignment, the measurement sensor 11 can accept the unique address
and listen to a communications bus for commands specific to the
individual sensor. A measurement control device 12 may send any of
the following commands to any of its connected sensors: (1)
connection check using the sensor's unique address; (2) Sensor LED
on/off; (3) Set sensor PWM output; (4) Read/Write sensor EEPROM;
(5) Measure Temperatures; and/or (6) Measure Radiation pulses for a
set time period (for example, one second). Other commands not
specifically listed can be sent by the measurement control device
12. After the measurement control device 12 sends a command to the
measurement sensor 11, the sensor performs the commanded action and
replies with a result if necessary.
[0143] In any number of embodiments of the system, when one or more
measurement sensors 11 are attached to a measurement control device
12 and the sensors are operational, the measurement control device
12 can indicate, through a message on the display screen, for
example, that the device is ready to begin data collection. When a
user begins data collection, the measurement control device 12
first downloads each sensor's individual calibration data and
stores the calibration data into control memory 40 or other desired
memory or storage. The control device 12 can then request for a
measurement of temperature and radiation pulses, for example, from
each attached measurement sensor 11. All received readings can be
stored, along with a time stamp, in the control memory 40, When the
control memory 40 might be full or if the user stops the data
collection, the measurement control device 12 may simply stop
accepting readings from the measurement sensors 11. A user may
download the saved data collected from the control memory 40 to a
computer or other desired storage.
[0144] In any number of embodiments, computer program code used in
the system may be capable of: (1) performing diagnostic tests on
the measurement control device 12; (2) transferring measurement
data from the measurement control device and saving it to a record
file; (3) gathering ancillary test data from the user or other
sources (radiation dose administered, test subject weight, PET scan
data, etc.) and including it in the data record file; (4)
transferring the data record file to the database server control
software; and (5) calculating the likelihood of an improperly
performed radioactive analyte injection and reporting or displaying
the same to a user, whether by audible, visual, or other signal. In
any number of embodiments, database server control software can
accept incoming data record files from the computer software and
apply one or more algorithms to the data received. Measurement data
may be stored in an optional central database 75 while the
algorithm output can be used to generate reports for the user.
These reports can indicate estimated parameters or even estimated
future parameters of a tumor.
[0145] In an embodiment of the system, for example, a user may
attach a measurement control device 12 to a computer and run
computer software to transfer measurement data stored on the
measurement control device 12 to the computer. The computer
software or program code communicates with the control device 12 to
determine what type and how much data is available for downloading.
The computer software can ask the user for pertinent test-related
information such as radiation dose administered, identification or
number of test subject 5, placement locations of the sensors, tumor
location and type, etc. Once measurement data has been transferred
from the measurement control device 12 to the computer, a data
record file can be built. Once complete, the data record file can
be transferred to a database server and predictive model or
algorithm system.
[0146] In any number of embodiments, pre-processing operations may
be performed on a test subject data set. Session measurements for
all channels can be normalized with respect to injected radiation
dose, for example. The dose is recorded during the test and is used
to adjust measurements on a scalar basis. A session is one specific
data recording event which includes sensor placement on the subject
5, injection of radioactive material, and collection, recordation
and transfer of recorded data. Measurements from each session can
be aligned so that the rising edge on a "trigger" channel--right or
left arm--is at time zero. The term "trigger" channel is used to
mean a sensor that is sure to see a large amount of radioactive
material so that it is ensured to have a dramatic and easily
recognizable increase in the measurement. Having a rapidly changing
"step" like this allows for time-alignment of data sets recorded at
different times or "sessions." Any data which is before a
predetermined time or after the predetermined time (for example,
data before time -120 seconds or after time 3600 seconds) can be
removed from the measurement data. In addition, session
measurements for all channels can be normalized with respect to
temperature sensitivity. Individual sensor's temperature correction
coefficients can be retrieved and used to correct the radiation
pulse count measurements.
[0147] In any number of embodiments of the system, session
measurements for all channels can also be adjusted to account for
the natural decay of the radioisotope used, for example. The
radioisotope naturally decays in the test subject and this adds a
decreasing function to the measurement data. Accounting for this
natural decay and removing any data attributed to the natural decay
can portray the data as the amount of radiation encountered without
the decay function included.
[0148] In any number of embodiments of the system 10, measurements
may be aligned with respect to the control channel(s). Control
channels are stable and repetitive, therefore aligning all channels
will make differences in the non-control channels visible.
[0149] In one embodiment of the system 10, a database server and
predictive model may be provided. A hardware server which runs
software to incorporate incoming data record files from the
computer software and to save this incoming data to a database file
along with data previously saved; and database server control
software. FIGS. 14 and 15, for example, illustrate flow diagrams of
operation of an embodiment of the computer software and the
database server control software respectively. The database server
and predictive algorithm system or model can apply one or more
algorithms to this saved database in order to estimate parameters
specific to the tumor under test or a group of tumors.
Additionally, the database server control software can apply one or
more models or algorithms in order to predict future parameters of
the tumor or a group of tumors. The database server control
software can also use the output of the algorithms to generate
report files for the user which present the estimated and/or
predicted parameters.
[0150] In an alternative embodiment of the system 10, a database
server and predictive model comprises a dynamic website with server
software running behind it, which allows for a multiple-user system
for analysis and reporting. In another embodiment, the database
server and predictive model or algorithm system further includes
functionality which transfers the algorithm output and report back
to the computer software for analysis and interpretation by the
user. In one embodiment, the database server and predictive model
further includes functionality which can provide real-time
communication and updates about sensor data; notification
parameters (e.g., situations with tumor development); and/or alert
conditions.
[0151] In an alternative embodiment of the system 10, database
server control software keeps a database of all measurement data
that has been submitted previously. Any new data record files that
are submitted can be added to the database. The user can include
other data records such as, but not limited to, results from other
tests (PET Scan, CT Scan, etc.), information about a particular
subject (height, weight, etc.), or general notes, for example. The
user can use the database server control software to generate
graphs of measured data, to calculate various functions of the
measured data and then graph those functions if necessary; and/or
to apply prediction algorithms to the data. The prediction model
may be capable of, although not limited to: (1) predicting the
future outcome of tumor treatments; (2) predicting which tumor
treatments have the best chance of success; (3) predicting the
likelihood that metastatic disease is present in the subject;
and/or (4) other. The database server control software can generate
reports for the user of measured data and/or predictions based on
the data. These reports include, but are not limited to, graphs,
predictions with confidence levels, etc.
[0152] In any number of embodiments of the system of the present
invention, the class of algorithms used is of the classification
structure in machine learning. These algorithms use a training set
of data to build a model of the data. Then, when new unknown data
sets are introduced, the algorithms can determine where in the
model the new data should fit. This approach allows for the system
of the present invention to inspect a submitted data set and
determine whether and how closely it has seen examples like the
submitted data set in the past. If there have been similar examples
in the past, the system can predict the outcome of the current data
set based on the outcomes of the past data. For example, if there
are various past examples that closely match the new data
submitted, the algorithm can determine which treatments in the past
led to the most favorable outcome. Physicians may then select
treatments with the best outcome. In another embodiment, the
algorithms can provide adaptive performance and measurement
capabilities. For example, if the rate of tumor growth accelerates,
the system can automatically respond to the change by increasing
sampling frequency.
[0153] In an embodiment of the system 10, the ways in which new
data submitted is matched to previously seen data or determined not
to match any of the previous data are based on multiple
mathematical or quantitative functions that can be applied to
measurement data. For example, area under the curve, polynomial
curve fit to a portion or all of the data, the ratio of two data
measurement channels, etc., are all ways in which data sets can be
matched,
[0154] Returning to the figures. FIG. 27 illustrates a detail of an
embodiment highlighting arm band 78, with fasteners 79, such as
hook and loop fasteners. Such an embodiment may combine measurement
sensor and controller on arm band 78. FIG. 28 is another embodiment
combined with arm band 78, with measurement sensor 11 and cable 24.
FIG. 29 illustrates a detail of light shield 28 with light shield
sealant 81.
[0155] FIG. 30 is a perspective exploded view of an aspect of an
embodiment, with light shield 28 having or defining light shield
scintillation cavity 28A and detector cavity 28B. Scintillation
crystal 20 and light detector 21 may thus fit within these
cavities, protected by light shield sealant 81. FIG. 31 is another
view of an embodiment of light shield 28, illustrating light shield
sealant 81 and optional collimator alignment light or LED 85. FIG.
32 is a cutaway of FIG. 31 illustrating an embodiment with relative
positioning of scintillation crystal 20, light detector 21 within
light shield 28. FIG. 33 is a further exploded view of that
embodiment, showing the inter-relation of the individual
components, with collimator alignment light 850
[0156] FIG. 34 illustrates an embodiment of measurement controller
12, with communication link 7, a plurality of controller
communications ports 47 and optional controller daisy chain port
46. FIG. 35 shows two daisy chained controllers.
[0157] FIG. 36 shows an embodiment of measurement sensor housing
25, with cable 24. FIG. 37 is an external view of another
embodiment of measurement sensor housing 25, with light shield 28
and sensor circuit board 23. FIG. 38 is a partial exploded view of
the FIG. 37 embodiment, illustrating light detector 21 and
scintillation material 20 with respect to light shield 28 and
sensor housing 25. FIGS. 39 and 40 show different sides of an
embodiment with a radiation shield alignment device 87 and
collimator alignment device 85. FIG. 41 illustrates radiation
shield 84. FIGS. 42-43 show details of radiation shield 84. In FIG.
44 is an external bottom side view of an embodiment of measurement
sensor 11 with radiation shield 84, with FIG. 45 showing an
exploded view of the same embodiment with components separated.
[0158] FIG. 46 is a cutaway view of an embodiment of measurement
sensor 11 attached to a radiation shield 84 defining a collimator,
with scintillation material 20 and light detector 21. FIG. 47 is a
cutaway view of another embodiment of measurement sensor 11,
illustrating optional collimator alignment device 85. FIG. 48 is a
further cutaway view of an embodiment with a different
configuration for collimator alignment device 85.
[0159] FIG. 49 is a perspective view of an embodiment of
measurement sensor 11 with measurement sensor stand 83. FIG. 50 is
a closer view of the embodiment of FIG. 49. FIGS. 51-52 show two
different perspective views of an embodiment detail with optional
radiation shield adjustment legs 97.
[0160] FIG. 53 illustrates an aspect of some embodiments, with two
measurement sensors 11 daisy chained with cable 24. FIG. 54 is
another embodiment in which a secondary measurement sensor 11 is
daisy changed to a primary measurement sensor 11 having shielding
mask 84. FIG. 55 illustrates various form factors for specific
embodiments of measurement sensor 11 having specific applicability.
FIG. 56 is an embodiment with an optional sensor trigger pushbutton
86.
[0161] FIG. 57 is a cutaway view of measurement sensor 11,
highlighting backscatter material 82. FIG. 58 details structure of
measurement sensor housing 25 serving as structure for backscatter
materials 82.
[0162] Some system 10 embodiments may be directed to the ex vivo
real-time detection of gamma radiation emitted by a subject from
administration and uptake over a period of time of a radioactive
analyte that decays in vivo by positron emission. These systems 10
may include at least one ex vivo measurement sensor 11, at least
one computer processor 42 (which may or may not be the same as
computer/processing station 70) having a non-transient memory 40
and a clock 48, the computer processor 42 in operable communication
with the measurement sensor 11, a temperature compensator 50, and
computer program code. An ex vivo measurement sensor 11 may have a
sensor housing 25, a scintillation material 20, a light detector
21, a temperature sensor 36, a signal amplifier 33, and a sensor
power source 32 (whether corded, battery, solar, etc). The light
detector 21, temperature sensor 36, signal amplifier 33, and sensor
power source 32 may generally be in operable communication. The
scintillation material 20 and light detector 21 may be disposed
within the sensor housing 25 in a light proof manner, with the
scintillation material 20 adapted to receive a level of gamma
radiation over the period of time from the in vivo radioactive
analyte and to emit photons representative of the gamma radiation
level. The light detector 21 may be disposed with respect to the
scintillation material 20 so as to receive and convert the photons
into signal data representative of the frequency level over time of
gamma radiation received. The signal amplifier 33 may be adapted to
amplify the signal data, the measurement sensor 11 having at least
one sensor output for such amplified signal data,
[0163] The at least one computer processor 42 may include a
non-transient memory 40 and a clock 48, with the computer processor
42 being in operable communication with the measurement sensor 11.
The memory 40 may have control computer program code executable by
the at least one computer processor 42. The control computer
program code may include a number of software modules, such as a
first module 61 for measurement, a second module 62 for data
management.
[0164] An optional temperature compensator 50 may be coupled with
the temperature sensor 36, such that the temperature sensor 36 is
adapted to measure an ambient temperature. The system 10 may thus
be adapted to communicate the ambient temperature to the
temperature compensator 50, so that the temperature compensator 50
may generate a temperature correction factor based on comparison of
the ambient temperature to a reference temperature. The temperature
compensator 50 further adapted to apply the temperature correction
factor to the signal data to produce temperature compensated signal
data.
[0165] The first module 61 may be adapted to receive the signal
data in a record file format, and the second module 62 may be
adapted to receive the signal data of a record file from the first
module 61 and to transmit the compensated signal data to a desired
storage. The computer program code 56 may further include a third
module 63 adapted to receive stored data of a record file from the
second module 62, and to apply such stored data to calculate
changes in the compensated signal data over a desired period. This
module may also apply stored data to a predictive model to generate
predictive data values over a desired period for such record file
as a predictive outcome, and to transmit such changes to a desired
storage, such as database storage 75.
[0166] Optionally, the ex vivo measurement sensor 11 may include a
radiation shielding mask 84 for gamma radiation. The shielding mask
84 may define an aperture in the form of a collimator 84c for gamma
radiation incident into the scintillation material 20. An alignment
feature 87 may be included for removable alignment of the
measurement sensor 11 with respect to the subject 5. In some cases,
the alignment, feature 87 may include a light emitter 85 disposed
within the sensor 11 so as permit alignment of the collimator
aperture 84c to a desired portion of the subject 5 by illumination
of the subject 5. Optionally, the light emitter 85 may be a light
emitting diode (LED) disposed within the aperture, and optionally
the ex vivo measurement sensor 11 may further include light proof
sealant 81 about the LED 85 to prevent the output of the diode or
ambient light to strike the scintillation material 20, while
permitting the scintillation material 20 to receive incident gamma
radiation.
[0167] Optionally, the ex vivo measurement sensor 11 may further
include a radiation shielding mask 84 for gamma radiation, with the
shielding mask defining an aperture in the form of a collimator 84c
for gamma radiation incident into the scintillation material 20;
and the system 10 may further provide a stand 83 as alignment
feature 87 for the removable mounting of the ex vivo measurement
sensor 11 in a configuration relative to the subject 5 so as to
permit alignment of the collimator 84c aperture to a desired
portion of the subject 5.
[0168] Optionally, the third module 63 may detect infiltration
conditions. In one approach, the third module 63 calculates changes
in the compensated signal data in order to determine infiltration
of radioactive analyte. In another approach, the predictive model
includes data representative of radiation frequency over time
associated with infiltration of the analyte within the subject for
determining an infiltration. Such a predictive model may include
data representative of spike of radiation frequency over time
associated with administration of the analyte for determining
proper administration of the analyte. An alarm or indicator may be
included to announce the determination of infiltration. Also
optionally, some embodiments may include an arm-band 78 for
removable affixation of the ex vivo measurement sensor 11 to an arm
of the subject 5.
[0169] Optionally, a filter in noise reduction 37 may be included
for filtering the amplified signal data based on amplitude. Such a
filter may be implemented with a voltage comparator. Alternatively,
the filter may comprises an analog to digital converter and control
computer program code adapted to compare digital amplified signal
data to a reference level.
[0170] A further system 10 embodiment may also be directed to the
ex vivo real-time detection of gamma radiation emitted at an area
of interest by a subject from administration and uptake over a
period of time of a radioactive analyte that decays in vivo by
positron emission. Such an embodiment may include a primary ex vivo
measurement sensor 11 and a secondary ex vivo measurement sensor
11. The primary ex vivo measurement sensor 11 may include a sensor
housing 25 with a radiation shield 84, the sensor housing 25 with
the radiation shield 84 defining a cavity, the radiation shield 84
further defining an aperture into the cavity as a collimator 84c
disposed within the aperture so as to admit a collimated gamma
radiation into the cavity from the area of interest, a
scintillation material 20 disposed within the cavity such that the
collimated gamma radiation is incident on the scintillation
material 20, a light detector 21 disposed within the sensor housing
25 to detect light emitted from the scintillation material 20, a
temperature sensor 36, a signal amplifier 33, and a sensor power
source 32. The light detector 21, temperature sensor 36, signal
amplifier 33, and sensor power source 32 in operable
communication.
[0171] In general, the scintillation material 20 and light detector
21 may be disposed within the sensor housing 25 with the
scintillation material 20 adapted to receive a level of gamma
radiation over the period of time from the in vivo radioactive
analyte, and to emit photons representative of the gamma radiation
level. As above, the light detector 21 may be disposed with respect
to the scintillation material 20 in a manner adapted to receive and
convert the multiplied photons into signal data representative of
the frequency level over time of gamma radiation received. The
signal amplifier 33 may amplify the signal data, and the
measurement sensor 11 may have at least one sensor output (e.g.,
port 27) for such amplified signal data.
[0172] In this embodiment, there is a secondary ex vivo measurement
sensor 11 that is unshielded for measuring background gamma
radiation, and a collimator alignment system 87 in operable
engagement with the sensor housing 25 for aligning the collimator
84c to the area of interest.
[0173] A temperature compensator 50 may be coupled with the
temperature sensor 36, such that the temperature sensor 36 is
adapted to measure an ambient temperature. The system 10 may thus
be adapted to communicate the ambient temperature to the
temperature compensator 50, so that the temperature compensator 50
generates a temperature correction factor based on comparison of
the ambient temperature to a reference temperature. The temperature
compensator 50 is further adapted to apply the temperature
correction factor to the signal data to produce temperature
compensated signal data.
[0174] The at least one computer processor 42 includes a
non-transient memory 40 and a clock 48, with the computer processor
42 in operable communication with the primary and secondary
measurement sensors 11. The memory 40 may have or store control
computer program code 56 executable by the at least one computer
processor 42, the control computer program code 56 may have a first
module 61 for measurement and a second module 62 for data
management. The first module 61 may be adapted to receive the
signal data in a record file format. The second module 62 may be
adapted to receive the signal data of a record file from the first
module 61 and to transmit the compensated signal data to a desired
storage (e.g., database storage 75). Also included may be third and
fourth modules 63, 64 of computer program code 56, the third module
63 adapted to receive stored data of a record file from the second
module, (i) to apply such stored data to a predictive model to
generate predictive data values over a desired period for such
record file as a predictive outcome, and to transmit such
predictive outcome to a desired storage; and (ii) to apply such
stored data to calculate changes in the compensated signal data
over a desired period, and to transmit such changes to a desired
storage and the fourth module 64 adapted to subtract signal data
from the secondary ex vivo measurement sensor 11 from signal data
from the primary ex vivo measurement sensor 11 having radiation
shield 84.
[0175] This embodiment may include the various options
corresponding to the options of the foregoing embodiments, though
as appropriate, for the shielded primary ex vivo measurement sensor
11. The secondary measurement sensor 11 remaining unshielded for
the detection of background radiation.
[0176] Some embodiments may specifically be directed to the
identification of proper or improper administration of the
radioactive analyte to the subject, including, but not limited to,
infiltration, for example. One such embodiment might be a system 10
for the ex vivo real-time detection over a period of time of gamma
radiation emitted by a subject 5 from the administration of a
radioactive analyte that decays in vivo. The parametric pattern of
data amplitude, slope, and/or time) from either or both proper and
improper administration may be used as reference data. The system
can compare the amplified signal data of an administration to this
reference data using a parametric model to determine the
probability of proper (or improper) administration of the
radioactive analyte to the subject.
[0177] In this case, system 10 may include at least one ex vivo
gamma radiation measurement sensor 11 to detect gamma radiation
over a desired period of time, and to produce signal data
associated with the desired period of time. The ex vivo measurement
sensor 11 may be adapted to sensing gamma radiation proximate to a
point of administration on the subject 5 of the radioactive
analyte. A signal amplifier 33 may be in operable communication
with the gamma radiation sensor 11 to amplify the signal data. As
above, the measurement sensor 11 may include at least one sensor
output or port for communicating such amplified signal data. The
data may be processed by at least one computer processor 42 in
operable communication or associated with a non-transient memory
40. Computer processor 42 may also be in operable communication
with the measurement sensor 11 via its output.
[0178] The non-transient memory 40 may have computer program code
56 executable by the computer or controller processor 42 to perform
the steps of receiving the amplified signal data with the desired
period of time, accessing reference data distributed over a
reference period of time, comparing the amplified signal data to
the reference data using a parametric model to determine the
probability of a proper administration of the radioactive analyte
to the subject 5. The computer program code 56 may be further
adapted to normalize the amplified signal data, and the parametric
model may be a time series function of one or more of the amplitude
and slope of the amplified signal data.
[0179] Embodiments may extend to a method 100 for the ex vivo
real-time detection over a period of time of gamma radiation
emitted by a subject from the administration of a radioactive
analyte that decays in vivo, as shown in FIG. 59. Such a method may
include the steps of (i) applying 100 an at least one ex vivo gamma
radiation measurement sensor 11 proximate to a point of
administration on the subject 5 of the radioactive analyte; (ii)
detecting 120 gamma radiation over a desired period of time and
producing signal data associated with the desired period of time;
(iii) amplifying 130 the signal data using a signal amplifier in
operable communication with the gamma radiation sensor, wherein the
measurement sensor having at least one sensor output for such
amplified signal data and outputting the amplified signal data;
(iv) processing 140 the amplified signal data using a computer
processor in operative communication with a non-transient memory
and the measurement sensor output by performing the step of: (a)
receiving 142 the amplified signal data associated with the desired
period of time; (b) from the nontransient memory, accessing 144
reference data distributed over a reference period of time; and (c)
determining 146 if the administration of the radioactive analyte
properly administered the radioactive analyte into the subject by
comparing the amplified signal data to the reference data using a
parametric model. Optionally, the processing 140 of the amplified
signal data may further comprises the step of normalizing the
amplified signal data. The parametric model may also be a time
series function of one or more of the amplitude and slope of the
amplified signal data.
[0180] A system 10 embodiments may include, but are not limited to,
an ex vivo measurement sensor 11 having a sensor housing 25, a
scintillation material 20 as a gamma radiation detector or sensor,
a light detector 21, a signal amplifier 33, and a sensor power
source 32. Light detector 21, signal amplifier 33, and sensor power
source 32 may be in operable communication. The scintillation
material 20 and light detector 21 may be disposed within the sensor
housing 25 in a light proof manner, with the scintillation material
20 adapted to receive a level of gamma radiation over the period of
time from the in vivo radioactive analyte and to emit photons
representative of the gamma radiation level. The light detector 21
may be disposed with respect to the scintillation material 20 to
receive and convert the photons into signal data representative of
the frequency level over time of gamma radiation received. The
signal amplifier 33 may amplify the signal data, the measurement
sensor 11 having at least one sensor output 27 for such amplified
signal data. At least one computer processor 42 may be associated
with a non-transient memory 40 and a clock 48, the computer
processor 42 in operable communication with the non-transient
memory 40 and the measurement sensor 11. The non-transient memory
40 may hold or include control computer program code 56 executable
by the computer processor 42 to receive the amplified signal data
in a record file format; transmit the amplified signal data to a
desired storage; access reference data from a desired storage; and
to apply such amplified signal data to a parametric model to
compare the signal data to the reference data to determine the
probability of a proper administration of the radioactive analyte
to the subject. As before, the amplified signal data may be
normalized, and the parametric model may be a time series function
of one or more of the amplitude and slope of the amplified signal
data.
[0181] Amplified signal data resulting from both proper and
improper administrations of radioactive analyte would both include
variability related to the total radioactivity of the radio analyte
as well as the method and process used for the injection. For
instance, the injection spike signal may have varying amplitude
depending on the total injected activity, or the rate of increase
of the amplified signal data would change based on the speed at
which the radio analyte is injected.
[0182] One approach to account for for the variances caused by the
above would be to normalize the amplified signal data based on the
maximum amplified signal value recorded. By scaling the amplified
signal data such that its scaled maximum value is, for instance, 1,
then various instances of amplified signal data could be compared
against each other even though their total injected activities may
differ. Another method, for example, of normalizing the amplified
signal data could be to scale the amplified signal data based on
the otherwise measured total activity of the injected radio
analyte.
[0183] With respect to the analysis or parametric model that may be
done with respect to the amplified signal data in order to
determine the likelihood or probability that administration of the
radioactive analyte is proper (e.g., accurate and consistent with
clinical protocol), the parametric model may include various
algorithms for comparing the amplified signal data to reference
data in order to calculate similarities or differences. As noted
above, the parametric model may be a time series function of one or
more of the amplitude and slope of the amplified signal data.
[0184] For the parametric model, one or more representative sets of
amplified signal data may be used as references that represent
administrations of radio analyte which were proper, whereas one or
more other sets of amplified signal data could be used as
references that represent administrations of radio analyte which
were improper. In one embodiment, for example, over a given portion
of the amplified signal data, a calculation may be made that would
sum the number of seconds during which the amplified signal data is
larger than a specified threshold value. For instance, in FIG. 24,
setting a threshold value of 500 would count only the time period
between 0 and 10. This desired amount of time that the amplified
signal data is higher than the threshold could be compared to the
same algorithm being applied to reference data. Then, the relative
similarity or difference in the calculated time of threshold
crossing would indicate the likelihood or probability that the
amplified signal data represents a proper or improper
administration of radio analyte to the subject.
[0185] Similarly, in another embodiment of parametric model,
instead of calculating the time period that the amplified signal
data surpasses a threshold, an integral of the amplified signal
data during the threshold surpassing time period may be calculated.
Then, applying this same algorithm to reference data will,
similarly, indicate the likelihood that the amplified signal data
represents a proper or improper administration of radio
analyte.
[0186] Additionally, a parametric model comprising a polynomial
could be statistically fit to the amplified signal data samples so
as to provide a best fit. The same order polynomial would be fit to
reference data sets as well. Then, the polynomial coefficients
could be compared in order to indicate the likelihood that the
amplified signal data represents a proper or improper
administration of radio analyte.
[0187] Also, an artificial intelligence neural network or cluster
analysis algorithm could be used as parametric models to compare
the amplified signal data to sets of reference data. These
algorithms would compare the amplified signal data to reference
data that is known to represent proper administrations and to those
that are known to represent improper administrations. The
algorithms would then indicate the likelihood that the amplified
signal data belongs to one of those groups.
[0188] It will be apparent to one skilled in the art that a
computer system that includes suitable programming means or modules
for operating in accordance with the disclosed methods also falls
well within the scope of the present invention. A specially
configured computer system including suitable programming means to
satisfy the objects described above can be provided. Suitable
programming means include any means for directing a computer system
to execute the steps of the system and method of the invention,
including for example, systems comprised of processing units and
arithmetic-logic circuits coupled to computer memory, which systems
have the capability of storing in computer memory, which computer
memory includes electronic circuits configured to store data and
program instructions, with programmed steps of the method of the
invention for execution by a processing unit. Aspects of the
present invention may be embodied in a computer program product,
such as a non-transient recording medium, for use with any suitable
data processing system. The present system can further run on a
variety of platforms, including any of a variety of software
operating systems. Appropriate hardware, software and programming
for carrying out computer instructions between the different
elements and components of the present invention are provided.
[0189] The invention may be embodied in other specific forms
without departing from the spirit or essential characteristics
thereof The present embodiments are therefore to be considered in
all respects as illustrative and not restrictive, the scope of the
invention being indicated by the claims of the application rather
than by the foregoing description, and all changes which come
within the meaning and range of equivalency of the claims are
therefore intended to be embraced therein.
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