U.S. patent application number 17/062327 was filed with the patent office on 2021-01-21 for methods of measuring head, neck, and brain function and predicting and diagnosing memory impairment.
The applicant listed for this patent is Stephanie Littell. Invention is credited to Stephanie Littell.
Application Number | 20210015420 17/062327 |
Document ID | / |
Family ID | 1000005123786 |
Filed Date | 2021-01-21 |
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United States Patent
Application |
20210015420 |
Kind Code |
A1 |
Littell; Stephanie |
January 21, 2021 |
Methods Of Measuring Head, Neck, And Brain Function And Predicting
And Diagnosing Memory Impairment
Abstract
A computer based method and system forms measurements of brain
function and predictions of a likelihood for memory impairment via
the use of cameras, including a near-infrared (NIR) spectroscopic
device and a camera capturing images in the Red-Green-Blue (RGB)
spectrum. The device acquires from a subject measurements of ions,
molecules, or combinations thereof at more than one moment in time,
as well as amplitude and timing of blood pulsations. Based on the
measured molecule or ion concentration, flow, and so forth, a
processor assesses the probability of a neuron to form an action
potential. Formation of an action potential increases the
probability that the subject individual will create a memory.
Inventors: |
Littell; Stephanie;
(Lexington, MA) |
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Applicant: |
Name |
City |
State |
Country |
Type |
Littell; Stephanie |
Lexington |
MA |
US |
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|
Family ID: |
1000005123786 |
Appl. No.: |
17/062327 |
Filed: |
October 2, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15306811 |
Oct 26, 2016 |
10791982 |
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PCT/US2015/028826 |
May 1, 2015 |
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17062327 |
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62092580 |
Dec 16, 2014 |
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61987626 |
May 2, 2014 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 5/14546 20130101;
A61B 5/7271 20130101; A61B 5/6898 20130101; A61B 5/746 20130101;
A61B 5/4088 20130101; A61B 5/1455 20130101; A61B 5/032 20130101;
A61B 5/021 20130101; A61B 5/14553 20130101; A61B 5/0261 20130101;
A61B 5/6814 20130101; A61B 5/031 20130101; A61B 5/168 20130101;
A61B 5/742 20130101 |
International
Class: |
A61B 5/00 20060101
A61B005/00; A61B 5/026 20060101 A61B005/026; A61B 5/03 20060101
A61B005/03; A61B 5/1455 20060101 A61B005/1455; A61B 5/16 20060101
A61B005/16; A61B 5/021 20060101 A61B005/021; A61B 5/145 20060101
A61B005/145 |
Claims
1. A method for predicting a likelihood for memory impairment in an
individual, the method comprising: a) using a near infrared
spectroscopic device on an individual at an anatomical region to be
studied; b) determining, with the device at the anatomical region,
a first measurement of at least one amino acid at a first time; c)
determining, with the device at the anatomical region, a second
measurement of the at least one amino acid at a second time; d)
comparing the first measurement to the second measurement; and e)
determining, based on the comparison of the first measurement to
the second measurement, a probability for one or more neurons to
generate an action potential, wherein the generation of an action
potential increases the probability of forming a new memory;
thereby predicting the likelihood for memory impairment in the
individual.
2. The method of claim 1, wherein the first time is a first moment
or a first time interval and the second time is a second moment or
a second time interval.
3. The method of claim 1, further comprising establishing a
baseline from one or more measurements of the at least one amino
acid at the first time, wherein the baseline represents a memory
map of the individual.
4. The method of claim 3, further comprising normalizing the memory
map based on the individual's age, gender, or other
characteristic.
5. The method of claim 1, wherein the at least one amino acid is
tyrosine or phenylalanine.
6. The method of claim 1, wherein the at least one amino acid is a
chemically-derivatized amino acid relating to dopamine.
7. The method of claim 6, wherein the chemically-derivatized amino
acid is L-dihydroxyphenylalanine (L-DOPA) or dopamine.
8. The method of claim 1, further comprising measuring cerebral
blood pressure, cerebral blood flow, cerebrospinal fluid pressure,
cerebrospinal fluid flow, intracranial pressure, or combinations
thereof.
9. The method of claim 1, wherein the region comprises a forehead
of the individual.
10. The method of claim 1, wherein the region comprises a frontal,
parietal, occipital, limbic, or temporal lobe of the
individual.
11. A computer system to predict a likelihood for memory impairment
in an individual, the system comprising: a measuring module
configured to determine a first measurement of at least one amino
acid at a first time, and configured to determine a second
measurement of the at least one amino acid at a second time; a
comparison module configured to receive and compare the first
measurement to the second measurement; and a probability module
coupled to the comparison module and configured to determine a
probability for one or more neurons to generate an action
potential, wherein the generation of an action potential increases
the probability of forming a new memory; from the determined
probability, the probability module forming a prediction of the
likelihood for memory impairment in the individual.
12. The computer system of claim 11, wherein the first time is a
first moment or a first time interval and the second time is a
second moment or a second time interval.
13. The computer system of claim 11, further comprising a baseline
module responsive to the measuring module and configured to
establish a baseline from one or more measurements of the at least
one amino acid at the first time, wherein the baseline represents a
memory map of the individual.
14. The computer system of claim 13, further comprising a
normalization module configured to normalize the memory map based
on the individual's age, sex, or other characteristic.
15. The computer system of claim 11, wherein the at least one amino
acid is tyrosine or phenylalanine.
16. The computer system of claim 11, wherein the at least one amino
acid is a chemically-derivatized amino acid relating to
dopamine.
17. The computer system of claim 16, wherein the
chemically-derivatized amino acid is L-dihydroxyphenylalanine
(L-DOPA) or dopamine.
18. The computer system of claim 11, further comprising a second
measuring module configured to measure cerebral blood pressure,
cerebral blood flow, cerebrospinal fluid pressure, cerebrospinal
fluid flow, intracranial pressure, or combinations thereof.
19. The computer system of claim 11, further comprising a device
module configured to operatively couple one or more infrared
spectroscopic devices to the measuring module.
20. The computer system of claim 19, wherein the infrared
spectroscopic device is a portable device.
Description
RELATED APPLICATIONS
[0001] This application is a continuation of U.S. application Ser.
No. 15/306,811, filed May 1, 2015, which is the U.S. National Stage
of International Application No. PCT/US2015/028826, filed on May 1,
2015, published in English, which claims the benefit of U.S.
Provisional Application No. 62/092,580 filed on Dec. 16, 2014 and
which claims the benefit of U.S. Provisional Application No.
61/987,626, filed on May 2, 2014. The entire teachings of the above
applications are incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] Maintaining a healthy brain is critical to overall health
and well-being. Early detection of disease or other threats to
brain health permits individuals to seek treatment sooner and,
ideally, provides individuals with a greater chance of reversal or
prevention of further declines in brain health.
[0003] Memory impairment and memory loss can be a result of
multiple etiologies. Commonly, Alzheimer's disease is a cause of
memory loss. However, short-term or long-term memory loss may be
caused by a number of other diseases and syndromes, such as
medications, drugs, trauma, infections, dementia, depression,
age-related, and stroke. Progression of memory loss or memory
impairment can be unsettling and debilitating. It is emotionally
difficult for a person having memory loss or impairment, and such
memory loss interferes with daily life. Memory loss or impairment
ranges from the occasional forgetfulness (for example, where car
keys were placed, whether medications were taken), to lack of
recognition of friends and family members.
[0004] Memory impairment and memory loss also affects spouses,
family members, relatives and friends who witness first-hand mental
and cognitive decline.
[0005] Typically, Alzheimer's disease is clinically diagnosed based
on family history and behavioral observations in a patient, for
example assessed through neuropsychological tests. Certain other
cerebral pathologies can be ruled out via MM or CT imaging
technologies. Definitive biological diagnoses of Alzheimer's
disease are currently possible only upon autopsy and analysis of
brain tissue, however, certain biomarkers for Alzheimer's disease
allow for a probable diagnosis. Amyloid protein plaques, for
example, are a biomarker of Alzheimer's disease and are detectable
in cerebral spinal fluid.
[0006] An adequate supply of oxygen and nutrients is critical for
normal brain function. Blood carrying oxygenated hemoglobin and
nutrients is delivered to the brain through the vascular system,
whereby pulsations of blood travel from the heart, through the
carotid and vertebral arteries, and ultimately through capillaries
where the exchange of water, oxygen, carbon dioxide and other
nutrients occurs between the blood and nearby tissues. Decreased
blood flow to a region of the brain may result in impairment of
that brain region's function. The interruption of blood flow to a
region of the brain of an individual may indicate that the
individual has suffered a stroke, a condition for which immediate
medical attention is required, even in the absence of outward
physical symptoms.
[0007] Frequently, medical attention for the diagnosis and
treatment of illnesses related to brain function is not sought
until after the manifestation of physical symptoms, such as memory
loss, impairment of speech, loss of consciousness, numbness, and
paralysis. In the absence of timely medical attention, lasting
disabilities or death may occur. The ability to visualize the
vasculature and circulatory function of the brain is not accessible
to the average individual, except through imaging studies conducted
by medical professionals, and, as stated above, individuals
frequently delay seeking medical attention until after the onset of
physical symptoms.
[0008] Therefore, there is a need for improved methods to monitor
brain function, health, and memory, and particularly for methods
which are accessible to the average individual. Additionally, there
is a need to detect decreased or interrupted blood flow before the
onset of physical symptoms. There is also a need for improved
methods to predict and diagnose a patient's level of memory
impairment and cognitive ability, and track a patient's memory loss
or impairment over time.
SUMMARY OF THE INVENTION
[0009] The present invention relates to methods of monitoring and
visualizing the vasculature system and circulatory function of the
brain, as well as other characteristics, enabling individuals to
monitor their own brain health. The present invention also relates
to methods of alerting individuals without significant medical
knowledge of potentially adverse changes in their circulatory
function in an easily comprehensible manner, prompting them to seek
early medical attention, if needed. The present invention further
relates to methods of predicting and diagnosing memory impairment
in an individual and to determining and monitoring the ability of
an individual to form new memories. In addition, the present
invention relates to computer systems and devices that aid in the
monitoring of brain function, health, and memory.
[0010] Accordingly, in one embodiment, the invention is directed to
a method for predicting a likelihood for memory impairment in an
individual. The method includes using a near infrared spectroscopic
device on an individual at an anatomical region to be studied. The
method also includes determining, with the device at the anatomical
region, a first measurement of each of one or more ions, one or
more molecules, or combinations thereof at a first time. The method
further includes determining a second measurement of each of the
one or more ions, one or more molecules, or combinations thereof at
a second time, and comparing the first measurement to the second
measurement of each of the one or more ions, one or more molecules
or combinations thereof. The method further includes determining,
based on the comparison step, a probability for one or more neurons
to generate an action potential, wherein the generation of an
action potential increases the probability of forming a new memory,
thereby predicting (or forming a prediction of) the likelihood for
memory impairment in the individual.
[0011] Another embodiment of the invention is directed to a
computer system to predict a likelihood for memory impairment in an
individual. The computer system includes a measuring module
configured to determine a first measurement of each of one or more
ions, one or more molecules, or combinations thereof at a first
time and configured to determine a second measurement of each of
the one or more ions, one or more molecules, or combinations
thereof at a second time. The computer system further includes a
comparison module configured to compare the first measurement to
the second measurement of each of the one or more ions, one or more
molecules or combinations thereof. The computer system further
includes a probability module coupled to the comparison module and
configured to determine a probability for one or more neurons to
generate an action potential, wherein the generation of an action
potential increases the probability of forming a new memory,
thereby predicting, or forming a prediction of, the likelihood for
memory impairment in the individual.
[0012] The first time, at which the first measurement is
determined, can be a first moment or a first time interval, and the
second time, at which the second measurement is determined, can be
a second moment or a second time interval.
[0013] The method can include establishing a baseline from one or
more measurements of one or more ions, molecules, or combinations
thereof at the first time. In certain embodiments, the computer
system further includes a baseline module configured to establish a
baseline from one or more measurements of the one or more ions,
molecules, or combinations thereof at the first time. The baseline
can represent a memory map, e,g, a local memory map, of the
individual.
[0014] The method can include normalizing the memory map based on
the individual's age, gender, or other characteristic. In certain
embodiments, the computer system includes a normalization module
configured to normalize the memory map. The measuring module can
include a baseline submodule and/or a normalization submodule.
[0015] The method can include assessing hypoxia, acidosis,
decreased ion flux, or combinations thereof, based on steps of the
method for predicting a likelihood for memory impairment. The
computer system can include an assessment module configured to
assess hypoxia, acidosis, decreased ion flux, or combinations
thereof. In some embodiments, a presence of hypoxia, acidosis,
decreased ion flux, or combinations thereof relates to an increased
likelihood of memory impairment. The comparison module and/or
probability module can be formed of or otherwise includes the
assessment module.
[0016] In embodiments of the method and computer system of the
present invention, the presence of hypoxia is determined by a
measured oxygen concentration (PaO.sub.2), a measured oxygen
saturation (O.sub.2 sat), a measured arterial oxygen content
(CaO.sub.2), a measured hemoglobin (Hb) concentration, or
combinations thereof.
[0017] In embodiments of the method and computer system of the
present invention, the presence of acidosis is determined by a
measured concentration of hydrogen (H.sup.+), bicarbonate
(HCO.sub.3.sup.-), carbonic acid (H.sub.2CO.sub.3), CO.sub.2,
phosphate (PO.sub.4.sup.3-, HPO.sub.4.sup.2-,
H.sub.2PO.sub.4.sup.-, H.sub.3PO.sub.4) or combinations
thereof.
[0018] In embodiments of the method and computer system of the
present invention, the measured ion comprises hydrogen (H.sup.+),
sodium (Na.sup.+), potassium (K.sup.+), calcium (Ca.sup.2+),
magnesium (Mg.sup.2+), chloride (Cl.sup.-), carbonate
(CO.sub.3.sup.-), bicarbonate (HCO.sub.3.sup.-), or a phosphate
(H.sub.3PO.sub.4, H.sub.2PO.sub.4.sup.-, HPO.sub.4.sup.2-, or
PO.sub.4.sup.3-).
[0019] In embodiments of the method and computer system of the
present invention, the measured molecule comprises a nucleic acid,
an amino acid, a sugar, a protein, a fatty acid, a nucleoside, a
nucleotide, or combinations thereof.
[0020] The protein can be hemoglobin; the amino acid can be any one
of glutamate and gamma-aminobutyric acid (GABA).
[0021] In other embodiments, the method includes measuring cerebral
blood pressure, cerebral blood flow, cerebrospinal fluid pressure,
cerebrospinal fluid flow, intracranial pressure, or combinations
thereof. In certain embodiments, the computer system includes or
the measuring module includes a second measuring module configured
to measure cerebral blood pressure, cerebral blood flow, or
combinations thereof.
[0022] In certain embodiments, the anatomical region includes a
forehead of the individual. In other embodiments, the region
comprises a frontal, parietal, limbic, occipital, or temporal lobe
of the individual.
[0023] In certain embodiments, the computer system includes a
device module configured to connect one or more infrared
spectroscopic devices. The device module can be operatively part of
the measuring module.
[0024] In embodiments of the method and computer system of the
present invention, the infrared spectroscopic device is a portable
device, such as a cell phone, tablet, phablet, laptop computer,
wearable aid, for example, a wristwatch, wrist cuffs, or footwear.
The device can also be a stand-alone device or at least one
mountable sensor that can be placed onto a body, or embedded into
clothing, bedding, or other devices. In certain embodiments, the
infrared spectroscopic device includes a built-in camera and
software for measuring the one or more ions, one or more molecules,
or combinations thereof.
[0025] In another embodiment, the invention is directed to a
computer-implemented method of measuring and displaying brain
circulatory function in an individual. The method includes using a
camera of a mobile device to capture a sequence of images at an
anatomical region of an individual, utilizing a digital processor
associated with the mobile device to process the captured images to
obtain volumetric, frequency, magnetic, and cycle time information
related to the pulsation and flow of fluid through the vessels and
cavities of the anatomical region of the individual, and to analyze
the information to obtain functional features relating to the
individual's brain circulatory system. The method further includes
rendering a graphical representation of the functional features of
the individual's brain circulatory system on a screen of the mobile
device.
[0026] In another embodiment, the invention is directed to a mobile
device for measuring and displaying brain, face, and neck
circulatory function in an individual. The mobile device can
include a camera configured to capture a sequence of images of an
anatomical region of an individual, a digital processor, and a
screen configured to render a graphical representation of
functional features of the individual's brain circulatory system.
The digital processor can be configured to process the images to
obtain volumetric, frequency, magnetic, and cycle time information
relation to the pulsation and flow of fluid through the vessels and
cavities of the individual, and to analyze such information to
obtain functional features of the individual's brain circulatory
system.
[0027] In embodiments of the method and device of the present
invention, the invention is directed to acquiring images in the RGB
(red-green-blue) visible light spectrum to capture images of the
vasculature of the face, head and neck. In another embodiment, the
invention is directed to acquiring images in the near infrared
spectrum to capture images of the vasculature beneath the skull.
The invention is also directed towards deducing functional features
of the vasculature including a frequency of blood pulsations
through a vessel, a volumetric change of a vessel, a concentration
of oxygenated hemoglobin, a concentration of deoxygenated
hemoglobin, rate of oxygen dissociation, and rate of nutrient
diffusion across a blood brain barrier. The mobile device of the
invention may be a wearable aid, cell phone, tablet, laptop
computer, or mountable sensor(s), for non-limiting example. Other
mobile or portable devices are suitable. The functional features
can be computed for each of a bilateral subsection of the
individual's anatomy and the functional features of each of the
subsections can be compared to assess a circulatory deficiency of
the individual. A cyclic vessel wall displacement, a vessel volume,
cyclic pressure, an angular velocity and a corresponding wave
energy can be estimated. The individual can be alerted to a
circulatory deficiency.
BRIEF DESCRIPTION OF THE DRAWINGS
[0028] The foregoing will be apparent from the following more
particular description of example embodiments of the invention, as
illustrated in the accompanying drawings in which like reference
characters refer to the same parts throughout the different views.
The drawings are not necessarily to scale, emphasis instead being
placed upon illustrating embodiments of the present invention.
[0029] FIG. 1 is a schematic view of embodiments measuring a head
and/or face area of an individual.
[0030] FIG. 2 is a flow diagram of one embodiment of the present
invention.
[0031] FIG. 3 is a graphical representation of a theoretically
isolated neuron's possible electrical gradient over time in the
presence of acidosis and/or hypoxia.
[0032] FIG. 4 is a flow diagram of one embodiment of the present
invention.
[0033] FIGS. 5A-5E are schematic illustrations of a user interface
for visualizing and manipulating brain, face, and neck circulatory
information.
[0034] FIGS. 6A-6C are schematic illustrations of a user interface
for further visualizing and manipulating captured brain circulation
information.
[0035] FIGS. 7A-7B are schematic illustrations of another user
interface in which related but disparate anatomy are represented in
the same display.
[0036] FIGS. 8A-8C are schematic illustrations of user interfaces
for displaying the transport of venous outflow and cerebrospinal
fluid.
[0037] FIGS. 9A-9D are schematic illustrations of user interfaces
for displaying representations of electrical brain activity.
[0038] FIG. 10 includes illustrations of easily-comprehensible
figures/icons representing pH, oxygen rippling, and energy.
[0039] FIGS. 11A-11D are schematic illustrations of an alternate
user interface for representing brain health in terms of electrical
activity.
[0040] FIG. 12 illustrates spin-pointer options.
[0041] FIG. 13 is a schematic view of a computer network embodying
the present invention.
[0042] FIG. 14 is a block diagram of a computer node in the network
of FIG. 13.
DETAILED DESCRIPTION OF THE INVENTION
[0043] A description of example embodiments of the invention
follows.
[0044] The generation of an action potential is required for the
formation of a memory in humans (mammals generally). Therefore, in
order to assess the ability of an individual to form a memory, or
alternately, in order to assess the likelihood for memory
impairment in an individual, the embodiments of the present
invention provide methods and apparatus for assessing the
probability of a neuron to generate an action potential.
[0045] Accordingly, in one embodiment, the invention is directed to
a method, systems and apparatus for predicting a likelihood for
memory impairment in an individual. An embodiment 100 illustrated
in FIGS. 1 and 2 includes using a near infrared spectroscopic
device on an individual (step 115 of FIG. 2) at an anatomical
region 10 to be studied. The computer-based system 100 is
initialized for the individual at 111 and started at 113 of FIG. 2.
The system 100 at step or module 117 determines, with the device at
the anatomical region 10, a first measurement of each of one or
more ions, one or more molecules, or combinations thereof at a
first time. Measuring module or step 117 further determines a
second measurement of each of the one or more ions, one or more
molecules, or combinations thereof at a second time, and a
comparison module or step 123 compares the first measurement to the
second measurement of each of the one or more ions, one or more
molecules or combinations thereof. The system/method 100 (through a
series of steps 119-125) assesses and eventually determines 127,
based on the comparison at 123, a probability for one or more
neurons to generate an action potential. The generation of an
action potential increases the probability of forming a new memory,
and thereby is a predictor of or forms a prediction of the
likelihood for memory impairment in the individual. Step 129 stores
an indication of the prediction (evaluation results) 127 as a
local-to-regional memory map.
[0046] "Memory impairment" as used herein, means any problem with
an individual's memory (e.g., a decline in an individual's ability
to form new memories or ability to recall formed memories). Memory
impairment can also refer to a deficit that is beyond the scope of
what would be anticipated or predicted in the normal course of
aging. Memory impairment can be assessed based on clinical
observation, neuroimaging, neuropsychological testing, and so
forth. In certain embodiments, an individual's memory impairment is
compared against, or fit into a spectrum of memory impairment
observed in other individuals, as stored in a library 120 for
example. Such multi-dimensional fitting could be stored in the
final memory evaluation 129 and used for further external
processing. Such a comparison, or such a spectrum, can include an
analysis of age, gender, education level, profession, physical
fitness, past medical history, or other characteristics of an
individual. In other embodiments, memory impairment is compared to
or assessed against (in module or step 127) another measurement or
prediction of memory impairment of the same individual, taken at an
earlier time point, for example, five years prior.
[0047] In certain embodiments, the time at which module or step 117
takes a measurement of ions, molecules, or a combination thereof is
a moment in time. In certain other embodiments, the time is an
interval of time. The interval of time can be selected based on
nutrient influx (e.g., Hb-O), or, alternatively, by arterial pulse
cyclicality as indicated or otherwise provided at 122.
[0048] An infrared spectroscopic device of module/step 115 measures
energy in the near-infrared (NIR) region of the electromagnetic
spectrum (energy having a wavelength from about 650 nm to about
1400 nm). In certain embodiments, the device is portable. A
spectroscopic device of 115 can be connected to, or be part of an
electronic processing device (e.g., cell phone, tablet, laptop
computer, portable digital processor device, or handheld computer)
50 of FIGS. 13 and 14. In certain other embodiments the
spectroscopic device at 115 further comprises a screen display or
monitor. In other embodiments, the spectroscopic device 115, 50
comprises a module for emailing or uploading data to a server 60
(FIG. 13), a computer connected to the Internet 70 (FIG. 13), or a
printer (or similar I/O devices). In other embodiments, the
spectroscopic device 50, 115 comprises a camera and programmed
processor for measuring one or more ions, one or more molecules, or
combinations thereof.
[0049] The anatomical region 10 that is studied in the methods and
systems of the present invention can lie anywhere along the surface
of the head as schematically shown in FIG. 1. In certain
embodiments, it is most efficient to begin with the prefrontal
cortex, which is often furthest from the cardiovascular supplying
arteries. The prefrontal cortex also contains the highest-level
integration of neuronal information, manifested as executive
functions. Other cerebral cortex regions may also be assessed.
[0050] In certain embodiments, the anatomical region 10 that is
studied is a forehead. Area 10 outlines the approximate region to
measure an ion concentration and/or flux. In certain other
embodiments, the region comprises a frontal, parietal, occipital,
limbic, or temporal lobe of the individual. The spectroscopic
device may also be used at more than one site on the individual.
For example, depending upon the results at one site, the user may
reposition the device to another cerebral region (generally 10), or
another head or brain region (generally 10) altogether.
[0051] As previously described in reference to FIG. 2, the method
and system 100 include the determination of a measurement 117 of
one or more ions, molecules, or combinations thereof. Such a
measurement 117 is taken at two or more times (e.g., 2, 3, 4, 5, 6,
7, 8, 9, 10, 15, 20, 25, 30, 50, 100, etc.), the measurements are
compared 123, and this comparison enables the determination 127 of
a probability for one or more neurons to generate an action
potential. The ability of a neuron to generate an action potential
increases the probability of forming a new memory.
[0052] In certain embodiments, the measured molecule is a nucleic
acid, an amino acid, a sugar, a protein, a fatty acid, a
nucleoside, a nucleotide, or combinations thereof.
[0053] In certain embodiments, the nucleic acid is a polymeric
macromolecule or biological molecule. Nucleic acids include
deoxyribonucleic acid, (DNA), ribonucleic acid (RNA), or artificial
analogs of nucleic acids.
[0054] In certain embodiments, the amino acid is a naturally
occurring amino acid or an artificial amino acid. Naturally
occurring amino acids include essential amino acids histidine,
isoleucine, leucine, lysine, methionine, phenylalanine, threonine,
tryptophan and valine. Non-essential amino acids include alanine,
arginine, asparagine, aspartic acid, cysteine, glutamic acid (or
glutamate, the deprotonated form of glutamic acid), glutamine,
glycine, ornithine, proline, selenocysteine, serine, and tyrosine.
Amino acids can also include synthetic amino acids, or chemically
derivatized amino acids, such as L-dihydroxyphenylalanine (L-DOPA).
In certain embodiments, the amino acid is gamma-aminobutyric acid
(GABA).
[0055] In certain embodiments, two or more amino acids are linked,
forming a polypeptide that is measured. In some embodiments, the
measured polypeptide is a protein. In certain embodiments, the
protein that is measured is hemoglobin.
[0056] Sugars measured by embodiments include monosaccharides,
disaccharides, and polysaccharides. Sugars can exist in linear
chain or cyclic configurations, and include, but are not limited to
glucose, sucrose, fructose, maltose, galactose, and lactose.
[0057] In certain embodiments, the fatty acid that is measured is a
carboxylic acid having a long saturated or unsaturated aliphatic
chain. Fatty acids include, but are not limited to, linoleic acid,
alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid,
oleic acid, elaidic acid, vaccenic acid, linoelaidic acid,
arachidonic acid, erucic acid and so forth.
[0058] A nucleoside comprises a nucleobase (e.g. adenine, guanine,
thymine, uracil, cytosine), bound to a 5-carbon sugar (e.g. a
ribose or a deoxyribose in a pentose conformation), via a
beta-glycosidic linkage. In example embodiments, the measured
nucleoside is cytidine, uridine, adenosine, guanosine, thymidine or
inosine, where the nucleoside contains either a ribose sugar
component or a deoxyribose component.
[0059] In certain embodiments, a nucleotide comprises a nucleoside
linked to one or more phosphate groups. In certain embodiments, the
nucleotide that is measured comprises ATP, ADP, GTP, CTP and UTP,
cGMP, cAMP, coenzyme A, FAD, FMN, NAD, or NADP+.
[0060] In certain embodiments, the measured ion is hydrogen
(H.sup.+), sodium (Na.sup.+), potassium (K.sup.+), calcium
(Ca.sup.2+), magnesium (Mg.sup.2+), chloride (Cl.sup.-), carbonate
(CO.sub.3.sup.-), bicarbonate (HCO.sub.3.sup.-), or a phosphate
(H.sub.3PO.sub.4, H.sub.2PO.sub.4--, HPO.sub.4.sup.2-, or
PO.sub.4.sup.3-).
[0061] The ability of one or more neurons to generate an action
potential is affected by conditions and parameters, as laid out in
detail below, an assessment of which occurs in module 123. These
conditions and parameters include: A. the concentration and flux of
ions, B. acidosis, C. the concentration and flux of certain
molecules, D. hypoxia, and E. cardiovascular parameters.
[0062] Returning to FIG. 2, the methods and apparatus 100 of the
present invention also provide for the assessment at module 127 of
hypoxia, acidosis, ion flux, or combinations thereof. Such an
assessment is based on using the near infrared spectroscopic device
115 to determine one or more measurements 117 (including a baseline
pattern 119) of one or more molecules, ions, or combinations
thereof. Specifically, hypoxia is determined to be present based
upon measured oxygen concentration (PaO.sub.2), oxygen saturation
(O.sub.2 sat), arterial oxygen content (CaO.sub.2), hemoglobin (Hb)
concentration, or combinations thereof. A measured concentration of
carbon dioxide (CO.sub.2) can also be useful in the detection of
chronic hypoxia because an elevated concentration of CO.sub.2 would
eventually not spur an increase in respiratory oxygen through to a
sensed region of the brain (through the vasculature and the blood
brain barrier to CSF at the brain stem). Oxygen in a healthy
individual would increase quickly (within approximately 1-3
seconds), in response to an elevated concentration of CO.sub.2, via
increased respiratory action. Although it is possible that an
elevated level of CO.sub.2 could initially manifest at the exact
time of testing in a healthy individual and before a corresponding
rise in O.sub.2, a detection of elevated CO.sub.2 is more likely to
indicate ineffective O.sub.2 delivery and/or chronic hypoxia.
Acidosis is determined to be present based upon measured
concentration of hydrogen (H.sup.+), bicarbonate (HCO.sub.3.sup.-),
carbonic acid (H.sub.2CO.sub.3), CO.sub.2, phosphates
(PO.sub.4.sup.3-, HPO.sub.4.sup.2-, H.sub.2PO.sub.4.sup.-,
H.sub.3PO.sub.4), or combinations thereof.
[0063] As discussed above, persons with memory impairment suffer
from a physiological inability or lowered ability to form new
memories. A neurological memory is a process in which patterned
input 124 is encoded, stored, and then later retrieved by an
individual. Memories are formed and stored when neurons generate an
action potential, for example a synaptic potential, or fire
sufficiently above the action potential threshold, traversing from
one presynaptic neuron to the next. Neurons manage electrochemical
gradients such that reasonably small amounts of various ions can
influence the cross-membrane potential. In an example embodiment,
an appropriate action potential generates, and is followed by, a
downstream recording event, or memory production.
[0064] Certain areas of the brain have been identified as being
involved in memory, function, and storage, including the cerebral
cortex, cerebellum, hippocampus, basal ganglia, amygdala, the
striatum, and the mammillary bodies. Certain areas of the brain are
thought to be involved in specific types of memory. For example,
the hippocampus is believed to be involved in spatial learning and
declarative learning, while the amygdala is thought to be involved
in emotional memory.
[0065] There are several types of memories that are implemented by
the brain in distinct ways. Working memory is the ability of the
brain to maintain a temporary representation of information about a
task that an animal or individual is currently engaged in. This
sort of dynamic memory is thought to be mediated by the formation
of cell assemblies or groups of activated neurons that maintain
their activity by constantly stimulating one another.
[0066] Episodic memory is the ability to remember the details of
specific events. This sort of memory can last for a lifetime. There
is evidence that implicates the hippocampus in playing a crucial
role in forming episodic memory. For instance, people with severe
damage to the hippocampus sometimes have amnesia, the inability to
form new long-lasting episodic memories.
[0067] Semantic memory is the ability to learn facts and
relationships. This memory is probably stored largely in the
cerebral cortex, mediated by changes in connections between cells
that represent specific types of information.
[0068] There are many diseases, conditions, and other reasons that
may cause memory impairment or loss, e.g., amnesia. Commonly,
memory impairment or loss is associated with Alzheimer's disease.
Other causes of memory loss or impairment may be from head trauma,
drugs, alcohol, infections (e.g., encephalitis, HIV, Lyme disease),
cardiovascular disorders (e.g., stroke, transient ischemic attack),
psychological disorders (dementia, depression), neurological
disorders (e.g., epilepsy, Parkinson's disease, Huntington's
disease, multiple sclerosis), cancer (e.g., brain tumor),
nutritional-deficiency (e.g., Vitamin B 12), and aging.
[0069] For an individual suffering from memory loss, or the
inability to form new memories, the study of certain chemicals in
the brain can provide insight into the conditions underlying memory
loss. As is detailed below, both Alzheimer's disease and conditions
that cause an inability for neurons to form an action potential
are, in certain embodiments, tracked or understood through analysis
of particular ions and molecules.
[0070] Alzheimer's Disease and Brain pH:
[0071] Studies into Alzheimer's disease have examined the
production of amyloid beta plaques and the role of amyloid beta
plaques in the progression of Alzheimer's disease. Amyloid beta
plaques are predominantly formed from mis-folded amyloid beta
peptides. Particularly, the presence of a .beta.-amyloid 42-residue
peptide chain (A.beta.42) indicates an Alzheimer's disease state
due to its fibrillogenicity. Typically, .beta.-amyloid 40-residue
peptide chains predominate in healthy subjects. The occurrence of
the .beta.-amyloid 42-residue peptide chains is often a late-stage
disease symptom.
[0072] Recent research has suggested that the soluble amyloid-beta
oligomer (A.beta.) disturbs synaptic function in earlier stages of
the disease. Hippocampus research suggests that A.beta. changes in
memory (NMDA) receptors affect downstream Ca.sup.2+ signaling
pathways, such as calcineurin and long-term potentiation kinase
CAMKII.
[0073] Research has also studied the amyloid precursor protein
(APP), the protein that is cleaved by alpha-, beta-, and
gamma-secretase to form amyloid peptide chains such as healthy
A.beta.40 or unhealthy A.beta.42. Intermediate peptide fragments,
for example C83 and C99, have been studied as well.
[0074] It is believed that beta-secretase (BACE1 enzyme) plays a
pivotal role in the generation of A.beta.42. Cleavage of APP by
BACE1 generates peptide fragment C99, which is cleaved by
gamma-secretase to form A.beta.42. Consequently, BACE1 inhibitors
have been considered as a potential treatment for Alzheimer's
disease. BACE1 also has optimal activity under acidic conditions at
around pH 4.5. Therefore, the generation of A.beta.42 can be
thought to proceed most efficiently when effective net [H+] is
increased 100 or 1000-fold from biological pH. Alpha-secretase
operates most efficiently at biological pH.
[0075] BACE1 is a transmembrane enzyme, whereas alpha-secretase is
in membrane. The former activates when extracellular pH is lowered
relative to normal intracellular pH.
[0076] In an example embodiment, in a person whose cardiac output
has slowed, blood does not pump up and all the way through the
cardiovascular system and into the far cerebral reaches of the
brain. Without sufficient oxygenated-hemoglobin vascular delivery
per every reasonably-timed cardiac cycle, the energy-producing
adenosine triphosphate (ATP) cannot produce energy as well.
Therefore, the extracellular solution increases in acidity with the
higher CO.sub.2 levels remaining present.
[0077] Extracellular acidity indicates that the fluidic
concentration of positively-charged ions (cations) relative to
negatively-charged ions (anions) has risen above biological range.
Cells invoke working mechanisms including ion channels and pumps to
try to restore homeostasis. However, cation:anion extracellular
ratios that might shift by 100 or 1000-fold (pH of 4.6-6.0)
relative to biological level impel cellular ionic influx/efflux,
and happen to be outside the tighter range of electrochemical
gradients that culminate in normal signals between neuronal
cells.
[0078] When extracellular chemical gradients are then driven
outside of their typical functioning ranges, the electrochemical
gradients for sending and receiving signaling are then affected
with varying probabilities depending on a number of factors, such
as state, degree of pH disruption, and time to recovery.
[0079] Therefore, examination of extracellular acidity provides an
indicator of BACE1 activity, thereby providing an early indicator
of probability to form amyloid plaques later in an individual's
brain.
[0080] Conditions that Affect the Formation and Propagation of an
Action Potential:
[0081] Conditions in the intracellular and extracellular space have
a profound impact on the ability of a neuron to generate an action
potential. In certain embodiments, ion concentrations and flux,
oxygen content, pH, the presence of other molecules, or
combinations thereof can all impact action potentials.
[0082] A. Ions, Ion Flux, Ion Channels, Ion Transporters:
[0083] The ability for a neuron to generate an action potential and
cause an input to be encoded and stored, for example, stored as a
memory, depends in part on the intracellular and extracellular
concentrations of certain ions.
[0084] In a normal (e.g., healthy) neural environment, potassium
ions (K.sup.+) contribute to the largest electrical component
cross-membrane, but are less concentrated in the extracellular
space than sodium (Na.sup.+), chloride (Cl.sup.-), and calcium
(Ca.sup.2+). See Table 1, below, for the extracellular and
intracellular concentrations of different ions.
TABLE-US-00001 TABLE 1 Respective concentrations of the following
ions and molecules in extracellular and intracellular fluids for
neurons at rest. Ion/Molecule [Extracellular] (mM) [Intracellular]
(mM) K.sup.+ (Potassium) 0.003 100 Na.sup.+ (Sodium) 140 10
Cl.sup.- (Chloride) 100 10 Ca.sup.2+ (Calcium) 2 0.00005-0.0001
H.sup.+ (Hydrogen) 4 .times. 10.sup.-4 7 .times. 10.sup.-5
Mg.sup.2+ (Magnesium) 1-2 0.5 HCO.sub.3.sup.- 21-29 8 glutamate
0.00002-0.03 1-100 HCO.sub.3.sup.- 25 10-20
[0085] Potassium alone causes a cell to have a -80 mV resting
potential, yet a neuron's membrane voltage adjusts slightly to
around -73 mV due to the electrical contributions of Na.sup.+ and
other ions, intracellular protein anion contributions, relative
ionic permeability, and combinations thereof. As calculated, the
contribution of K.sup.+ ions to effective mV could constitute
.about.91% in resting state.
[0086] At low pH, for example as in acidosis, the Na.sup.+/K.sup.+
pump operates to rectify the pH. However, since acidosis correlates
with decrease in oxygen delivery, ATP production is affected.
Therefore, the Na.sup.+/K.sup.+ pump, with decreased ATP available,
is unable to maintain normal, physiologic extracellular and
intracellular ion concentrations.
[0087] At this stage, ATP is no longer available to the cell to
maintain healthy electrochemical gradients cross-membrane; the net
movement of ions in the present electrical field due to chemical
gradients and the osmotic movement of molecules through the cell's
semipermeable membrane will start to spontaneously occur.
[0088] K.sup.+ ions will efflux to rectify chemical imbalance
between acidosis and hypoxia, while Na.sup.+ ions influx. Other
concentrations of ions also adjust. Without ATP energy delivery,
the Na.sup.+/K.sup.+ concentrations would become effectively
reversed. A neuron becomes depolarized, achieving, for example, a
potential of about +73 mV, or more, the potential depending upon
immobile residual intracellular protein, ions and combinations
thereof. The membrane potential in certain embodiments is lower, as
various ions influx and/or efflux, and and weaker forces start to
dominate. For example, weaker forces include intermolecular forces
such as dipole forces and Van der Waals forces.
[0089] When ATP production ceases, most ion pumps also cease. By
contrast, Transient Receptor Potential Mediator 7 (TRPM7) activates
current immediately when ATP is omitted. TRPM7 contains both an ion
channel and a kinase domain, and selectively transports divalent
cations such as Ca.sup.2+ and magnesium (Mg.sup.2+) among other
metals. It is strongly activated when ATP decreases to less than 1
mMol.
[0090] Generally Mg.sup.2+ is reported to inhibit TRPM7, but
without available ATP, free Mg.sup.2+ at biological concentration
of 720 .mu.M permeates the cell via influx. Mg.sup.2+ current is
greater than Ca.sup.2+ through this channel.
[0091] TRPM7 is found in virtually every mammalian cell, although
in different amounts. It is estimated that there are 10-100
channels per cell. The TRPM7 channel can serve to amplify
excitatory postsynaptic potentials (EPSPs) through presynaptic
vesicle release. The sum of individual EPSPs have a combined effect
resulting in a larger EPSP, absent inhibitory neurotransmitters.
The larger EPSPs result in greater membrane depolarization and
increase the likelihood that the postsynaptic cell reaches the
threshold for firing an action potential, necessary for encoding a
memory. So far, larger EPSPSs seem only to be found in sympathetic
neurons and at neuromuscular junctions where acetlycholine
neurotransmitter is used.
[0092] B. Acidosis (pH)
[0093] pH can be considered as a measure of the acidity or basicity
of an aqueous solution, with acidic solutions having a pH less than
7, and basic solutions having a pH greater than 7. The pH of blood
is usually between 7.35 and 7.45, and is referred to herein as
physiological pH or biological pH. However, the pH in other
biological compartments can vary, e.g., the gastric acid in a
stomach has a pH around 1 and pancreatic secretion has a pH around
8.
[0094] pH is defined as the decimal logarithm (base 10) of the
reciprocal of the hydrogen ion (H.sup.+) in a solution, written
as:
pH=-log.sub.10[H.sup.+]
[0095] pH also relates to acid/base relationships and electron
donor/acceptor relationships.
[0096] Human neurons function in a relatively specific pH range of
approximately 7.1 to 7.3 (Srinivasan, et al., pH-Dependent Amyloid
and Protofibril Formation by the ABri Peptide of Familial British
Dementia, Informa Healthcare, 11:1; 10-13 (2004), the relevant
teachings of which are incorporated herein by reference in their
entirety). An atypical shift in pH, for example, would cause
neurons to immediately and automatically take measures to
counteract the change, trying to restore the pH to biological pH
levels in order to maintain function. For instance, astrocytes
(astroglia) use a carbonate buffering system to manage
extracellular pH.
[0097] A drop in pH, or acidosis, in the brain is undesirable,
causing neuronal cells to alter their normal functioning in order
to correct any such imbalance. Acidosis can arise regionally
(locally) or encompass the entire brain (globally). Causes of
acidosis include hemorrhage, arterial blockage leading to poor
cerebral circulation, respiratory insufficiency or other factors,
and acidosis can lead to stroke and/or death.
[0098] A neuron responds to its immediate environment, including
the extracellular space. The extracellular space is less voluminous
relative to the volume and size of a neuron (made up of axon,
dendrites, soma etc.). A regional change (e.g., in pH) can affect
one or just a few neurons. Even more localized changes (e.g., in
pH) may only affect a single dendrite or a side of an axon.
[0099] The methods and apparatus described herein include assessing
pH changes in the brain. These changes may be regional or global pH
changes. As described above, the pH changes may involve a single
neuron, or multiple or a group of neurons. Determining where
acidosis is occurring in the brain can aid in determining or
predicting a likelihood of memory impairment in an individual. The
system modules/steps 117, 119, 121, 122, 123, and 125 (FIG. 2)
provide for tracking, monitoring, and mapping pH values over
time.
[0100] Furthermore, as discussed above, the activity of BACE1 is
optimized under acidic conditions of about pH=4.5. With increasing
BACE1 activity, the probability of later amyloid plaque formation
is increased.
[0101] C. Presence and Concentration of Molecules:
Neurotransmitters, Drugs, Other Chemicals
[0102] As described herein, an array of molecules and ions are
measured 117 to afford this insight into memory formation. For
example, the molecules and ions can include neurotransmitters,
drugs, chemicals, receptors, and so forth. In an example
embodiment, N-methyl-D-aspartate (NMDA) receptor is measured. NMDA
is involved in controlling memory and learning. In order to map an
action potential, both ligand-ion-channel and voltage gating must
take place simultaneously.
[0103] In certain embodiments, a magnesium ion is measured at 117.
An Mg.sup.2+ ion blocks the receptor channel in a voltage-dependent
manner. Current state-of-the-art states that it is rolled away when
the cell depolarizes.
[0104] In certain other embodiments, ATP is measured at 117.
Without ATP, cross-membrane flux between resting potential and +50
mV or more depolarization may be occurring. The TRPM7 channel can
be activated and removes Mg.sup.2+ blockage of NMDA receptor.
Without ATP, the glutamate transporter direction depends upon the
ion gradient. Glutamate can be released instead of removed from the
synapse.
[0105] According to embodiments, voltage may also be calculated
according to the equation:
Effective voltage=A sin(.omega.t+.PHI.)
where A is amplitude, .omega. is angular frequency (.omega.=2.pi.f;
where f is frequency), t is time, and .PHI. is phase.
[0106] D. Hypoxia (O.sub.2):
[0107] Periods of hypoxia cause depolarization of neuronal
membrane, which ultimately ceases the action potential discharge,
or firing activity, of the neurons. While brief periods of hypoxia
can cause reversible depolarization of the neuronal membrane,
longer periods of hypoxia contribute to irreversible depolarization
(Calabresi, P., et al., On the mechanisms underlying
hypoxia-induced membrane depolarization in striatal neurons, Brain,
118 (Pt 4):1027-38 (1995), the relevant teachings of which are
incorporated herein by reference in their entirety).
[0108] As illustrated in the graph of FIG. 3, a theoretically
isolated neuron has an attenuating electrical gradient 300 over
time in the presence of acidosis and/or hypoxia. Other curves are
possible, for example where the decay rate, angular frequency,
phase, amplitude and/or recovery time window is varied. The graph
is similar to a damped sine wave, which is a sinusoidal function
whose amplitude 310 approaches zero as time increases. When ATP
becomes no longer available to power the cell's maintenance of
gradients at start time on the graph, for example, the cell
(neuron) might happen to be in its resting phase or approximately
-70 mV (millivolts).
[0109] E. Cardiovascular Effects (Blood Flow, Blood Pressure,
Etc.)
[0110] Blood carries and transfers nutrients through the epithelial
cell barrier that lines cerebral microvessels (commonly called
"blood-brain barrier"). Nutrients in blood such as bicarbonate,
K.sup.+, Na.sup.+, and water transport through the blood-brain
barrier to the circulating extracellular fluid (ECF). Interstitial
fluid (ISF), although cyclically-slower than blood flow, bathes the
surrounding neurons. Interstitial or extracellular spaces are tight
and can be further congested with extracellular networks, other
cells and transmembrane protuberances. Due to these reasons, ion
concentrations may sometimes vary by locale.
[0111] The effective transfer of nutrients and ions from each fluid
compartment to the next effectively diminishes. The movement of
ions and nutrients slows from the blood to the ECF or ISF proximate
to the neuron sublocale where needed. Via water flux and
osmolarity, blood flow and pressure become the driving force for
CSF formation (by the choroid plexus epithelial cells) and nutrient
transmission, to enable the cell's electrical duties and to power
sufficient gradients above action threshold when needed.
[0112] Memory Evaluation
[0113] As described herein, embodiments of the invention relate to
a tool 100 (FIG. 2) that recognizes any such "real-time" acidosis
and/or hypoxia. As will be apparent to one of skill in the art, the
methods and apparatus described herein can be useful in cases of
hypoxia, diabetes, cerebral infarction, arterial stenosis, decline
in cardiac output, insufficient O.sub.2 delivery performance from
oxygenated-hemoglobin, or periods of postural stasis that
exacerbates low rates of oxygen unloading or waste removal.
[0114] In certain embodiments, the methods and apparatus 100
further include establishing a baseline 119 from the first
measurement of each of the one or more ions, molecules, or
combinations thereof at the first time, and utilizing a library of
ion/molecule spectrum pattern profiles 120. That baseline
measurement 119 provides a memory map 121 of the individual. As
used herein, "memory map" refers to a correspondence duality
defined between memory and spatial regions. In some ways, a memory
map is similar to a highway or road map, where a memory map
represents an individual's aspects of memory against his brain
regions. A memory map 121 can also contain information regarding a
hierarchy in memory strengths and memory weaknesses, types of
memory processed, anatomical delineations, branching, density of
storage, etc. In certain embodiments, the memory map 121 is
normalized based on gender, age, diet, height, weight, medical
history, race, environmental factors, genetic dispositions,
athletic level or ability, cardiovascular profile, or other
physical, mental, social, or any other characteristic of the
individual. A memory map can be represented at high-level
(regional) or low-level (molecular, ion) detail.
[0115] Another embodiment of the invention is directed to a
computer system 100 to predict a likelihood for memory impairment
in an individual. The computer system comprises a measuring module
117 (FIG. 2) configured to determine a first measurement of each of
one or more ions, one or more molecules, or combinations thereof at
a first time and configured to determine a second measurement of
each of the one or more ions, one or more molecules, or
combinations thereof at a second time (subsequent to the first
time). The computer system 100 further comprises a comparison
module 123 configured to compare the first measurement to the
second measurement of each of the one or more ions, one or more
molecules or combinations thereof. The comparison module can
provide an updated memory map 125 including information regarding
propagation delay. The computer system 100 further comprises a
probability module 127 coupled to the comparison module 123 and
configured to determine a probability for one or more neurons to
generate an action potential, wherein the generation of an action
potential increases the probability of forming a new memory. In
that way, probability module 127 predicts the likelihood for memory
impairment in the individual (forms such a prediction based on
determined probability) by evaluating changes against thresholds
and prior patterns.
[0116] In a preferred embodiment, memory maps 121, 125 can be
low-level memory maps, representing specific spatial trajectories.
Memory map 129 can be a high-level memory map, permitting users to
see a simplified, regional view. Memory maps 121, 125, 129 can
include and represent data in a three-dimensional manner.
[0117] In certain embodiments, the computer system 100 further
comprises a baseline module 119 configured to establish a baseline
from one or more measurements of the one or more ions, molecules,
or combinations thereof at the first time. That baseline
measurement 119 provides a memory map 121 of the individual, as
described above. In further embodiments, the computer system 100
also comprises a normalization module configured to normalize the
memory map 121 based on gender, age, diet, height, weight, medical
history, race, environmental factors, genetic dispositions,
athletic level or ability, cardiovascular profile, or other
physical, mental, social, or other characteristics of the
individual. In some embodiments the measuring module 117 includes a
baseline submodule and/or normalization submodule.
[0118] The present invention also provides for the computer system
to further comprise an assessment module 127 configured to assess
hypoxia, acidosis, ion flux, or combinations thereof. When hypoxia
or acidosis is present or when ion flux is accordingly increased or
decreased, the likelihood for memory impairment is increased. In
some embodiments the comparison module 123 and/or probability
module 127 is referred to as an assessment module.
[0119] In certain embodiments, the computer system 100 further
comprises a second measuring module configured to measure cerebral
blood pressure, cerebral blood flow, or combinations thereof. In
some embodiments the measuring module 117 is further configured to
measure cerebral blood pressure, cerebral blood flow, or
combinations thereof Measurements of cerebral blood pressure and
cerebral blood flow can provide useful context for other
measurements, such as ion flux.
[0120] The present invention provides for the computer system to
further comprise a device module 115 configured to connect one or
more infrared spectroscopic devices 115, 50. In some embodiments,
the device module 115 is operatively part of the measuring module
117.
[0121] In certain embodiments, the present invention enables the
discovery of new regions of memory loss. In alternate embodiments,
the invention identifies new regions of memory loss with high
probability. For example, the invention can produce a visual image
depicting concentration and migration of a target ion, for example
Mg.sup.2+ or K.sup.+. In a further embodiment, an assessment of the
total effective ion gradient is produced by steps/modules 119-125,
which can suggest (by module/step 127) whether the gradient is
fluctuating sufficiently to generate a threshold action potential
value.
[0122] System 100 also allows for flagging or sending an alert 130
if a region is designated (or determined) to have or to potentially
have memory loss. Such an alert can also indicate the locale of the
region at risk. The alert is sent (by module/step 130) to the
individual, the individual's designated devices or wearable aids, a
member of the individual's family, an individual's health proxy, a
healthcare provider, one or more persons designated by the
individual, or a combination thereof. In certain embodiments, the
computer apparatus/system 100 at 130 automatically triggers an
alert, for example as an email, a banner, or other electronic
communication, to be sent to the designated recipient. In another
embodiment, the report/alert module 130 correlates future risk of
memory loss in a region against threshold action potential.
Report/alert module 130 can also provide an alert to the user to
obtain a future measurement and can also report out the results to
the user or a third party. The user may repeat the process (steps
115-130) repeatedly over time to acquire long-term trends, as shown
in step 135.
[0123] In certain embodiments, the present invention enables the
discovery of existing pockets of previously lost neurons, or lost
memory. In an example embodiment, module/step 127 identifies such
regions through tracking ion flow; any regions of relative ion flow
trajectory silence can be indicators of previous neuronal apoptosis
or necrosis, or can indicate glial cleanup.
[0124] Ion and molecule concentration are useful to assess because
these are signaling enablers that correlate to healthy range of
memory function. Furthermore, in regions having a low pH, potassium
or calcium can be the largest contributor to wrong signaling
scenarios.
[0125] New regions of memory loss and existing regions of
previously lost neurons can be discovered and assessed based on a
number of measureable parameters. In certain embodiments, these
measureable parameters include the effective rate of oxygen
unloading, measured, for example as oxygen concentration per unit
time or per cardiac cycle at 122. In another embodiment, oxygenated
hemoglobin concentration ([HbO]) per unit time or per cardiac cycle
is measured at 122. In another embodiment, the measureable
parameter includes rate of ATP production. In another embodiment,
hydrogen ion concentration is measured per unit time or per cardiac
cycle at 122.
[0126] In the above embodiments, if the concentration is below some
previously indicated threshold, an alert or flag is raised, as
described in the methods (report/alert module 130) above. The
previously indicated threshold in module 127 can be designated by
the computer application/system 100, by the individual, by the
user, by a health care professional and the like.
[0127] In alternate embodiments, pH is detected, or alternately
determined from the measurements of ion concentrations 117 or from
bicarbonate buffering system measurements (e.g. bicarbonate,
carbonic acid). In certain embodiments, pH detection provides an
evaluation of signal strength, memory retention, memory recall,
depth of neuron branching, and energy storage via capacitance (e.g.
delta charge, charge state).
[0128] In certain embodiments, as illustrated at step 124 in FIG.
2, an input image is supplied to a user. Through the input image,
the computer system/apparatus 100 (modules 117-129) or the user can
track ionic flux, trajectories of ions, lack of ions or target
molecules in a particular subregions, changes in pH, hypoxia or
ischemia, or other information.
[0129] The invention displays on screen and/or provides a report in
which the likelihood for memory loss is reported or otherwise
output 130 to the individual or user. As discussed above, the
display/report optionally comprises a comparison against memory
impairment observed in other individuals, or alternately provides a
spectrum on which an individual's memory impairment is ranked. Such
a comparison, or such a spectrum, can include an analysis of age,
education level, physical fitness, or other characteristics of an
individual. In other embodiments, memory impairment is compared to
or assessed against another measurement or prediction of memory
impairment of the same individual, taken at an earlier time period
(date), for example, five years prior.
[0130] Circulatory Evaluation
[0131] The frequency and volume of pulsations of blood through the
vessels of the brain are directly related to the oxygenation of,
and nutrient delivery to, brain tissue. Therefore, in order to
assess the function of an individual's brain circulation,
embodiments of the present invention provide methods and apparatus
for measuring the frequency and volume of blood pulsations or flow
through brain vessels and methods for analyzing such information in
order to obtain functional features of the individual's brain
circulation. Both arterial and venous vasculature can be captured
and measured. Additional information pertaining to an individual's
cerebrospinal fluid flow may also be measured and presented.
[0132] Utilizing a mobile device equipped with a camera, a user of
the device can capture a series of images of the individual's face,
head, and neck regions. The user of the device can be the
individual. A camera capturing images in the RGB (red-green-blue)
spectrum of visible light provides information on the vascular
pulsing and progression of blood through blood vessels travelling
beneath the subject's skin. A camera capturing images in the
near-infrared spectrum captures similar information of the
vasculature contained beneath the skull of the individual. By
capturing a sequence of images over a period of time, frequency and
volume of blood pulsations and flow are measured. Such pulsation
and flow information is reconstructed and graphically represented
to the user through an animated and touch-sensitive user interface.
In one embodiment, the graphical representation includes a map of
the individual's vasculature. In another embodiment, a generic
representation of the vasculature of the brain and face of a human
is displayed, with subject-customized pulsation animation
superimposed onto the generic graphics. Various representations of
blood and/or nutrient transport to the brain can be depicted, in
addition to other information, such as the flow of cerebrospinal
fluid.
[0133] Accordingly, embodiments of the invention are directed to a
method, system and apparatus for capturing and presenting
circulatory information relating to the pulsation and flow of
fluid, including blood and CSF, within an anatomical region of an
individual. An embodiment 400, illustrated in FIG. 4, includes
positioning a mobile device (step 405) having at least one camera
equipped to capture photographs in the RGB and near-infrared
spectrum in front of the face, head, and/or neck of the individual,
e.g. the user. The mobile device captures a sequence of images of
an anatomical region of the user, as shown in step 410. The
circulatory information provides information relating to
volumetric, frequency, cycle time and magnetic behavior (step 415),
including, for example, changes in the volume of a vessel, changes
in the frequency of blood pulsations through an artery, and changes
in the flow of fluid through a vein or sinus cavity. This
information is analyzed (step 420) to produce functional features
of the user's circulation (step 425), which is rendered graphically
on a screen of the device for user viewing (step 430). Graphical
rendering (step 430) can include and represent data in a
three-dimensional manner. The user is then able to navigate through
a mapping of the user's vasculature while viewing real-time
information relating to volumetric, frequency, cycle time and
magnetic behavior (step 435). Additionally, the user can be alerted
to brain health status, including any potentially negative markers
of brain health (step 440). The user may repeatedly capture images
to acquire long-term trends (step 445), in which case the mobile
device captures additional data points and the user can be provided
with additional and historical data relating to the user's brain
health.
[0134] FIGS. 5A-5E schematically illustrate a user interface 500
for visualizing and manipulating brain circulatory information.
FIG. 5A illustrates the region(s) captured by the camera of the
subject 520 and depicted on a display 510 of the device screen,
along with user-selectable viewing modes 525, including "Transport"
mode 530, "Brain" mode 535, "Compare" mode 540, and "Pics" mode
545. Vasculature 550, 555 of the subject can be made visible,
either through generic representations of vessels or through a
reconstruction of the subject's own vasculature following imaging.
In FIG. 5A, the Transport 530 viewing mode is shown to be selected
and highlighted, representing the circulatory function of the
subject's brain, head, and neck. Other viewing modes 525 are shown
dimmed. The vasculature 555 of the subject 520 can be displayed
with a precise line to indicate an oxygenated vessel, or a vessel
for which an adequate amount of imaging data has been captured.
Vasculature 550 can be displayed with a dimmed or less precise line
to indicate a less-oxygenated vessel, or to serve as a default
representation until an adequate amount of imaging data has been
captured.
[0135] As the camera continues to capture imaging data in the RGB
and near-infrared spectrums, additional vasculature 560 may
populate on the display 510, as shown in FIG. 5B. The depicted
vasculature can pulsate to indicate an active artery, or in
correspondence with the subject's pulse. Audio tones or vibrations
may pulse synchronously as well. A compendium of fluidic pulsations
which cyclically expand the cranial space can appear with a pulsing
surround 562. Some facial and skull bones, particularly finer
bones, articulate in order to accommodate pulsational flow. Such
articulation can have a lateral average of about 2 mm, which can be
detected by dynamic sequencing of images.
[0136] As additional detail regarding the vasculature is captured
and displayed, facial features may recede from view and zooming may
occur, as depicted in FIG. 5C. Vasculature 560 can be displayed
with a blurring effect as a means to display relative motion of the
vessel. For example, edges may be represented with a lighter,
blurred effect to represent areas where a vessel wall spends less
proportional time, while a central area are of the vessel can be
represented with a darker, solid effect. Volume changes in the
vessel can be imputed from the detected pulsations. Additionally, a
rate of volume change over time can be calculated. Some facial
features, such as eyebrows 570 and eyes 575 can remain for the user
to maintain a sense of orientation. In addition, or alternatively,
an icon 580 can be displayed depicting a face to indicate the
present view, or stage within the Transport mode, to the user.
Additionally, continuity between the RGB and near-infrared images
can be achieved by using features such as eyebrows 570 and eyes 575
as markers. Vasculature behind the skull, captured with the
near-infrared camera, and vasculature behind soft tissue, captured
with the RGB camera, must be aligned both spatially and cyclically
to provide for oxyhemoglobin correspondence and delay, as well as
for visualization purposes.
[0137] As shown in FIG. 5D, cardiovascular network regions can be
touch-sensitive and, upon selection by the user 595, the display
510 may responsively highlight a selected vessel 590 and provide
the user with a further zoom view or additional information
regarding the selected vessel. If the viewing camera has shifted
during the active capturing of images of the subject's anatomy, a
re-view may be suggested to the user, or prior cycle data
previously captured may be substituted.
[0138] As shown in FIG. 5E, cardiovascular network regions may be
swipe-sensitive, and upon selection by the user 595, the next
Transport stage may be invoked. As shown in FIG. 5E, a user swipes
along a vessel of interest 590. The next Transport stage then
appears, as further described with respect to FIGS. 6A-6C
[0139] FIGS. 6A-6C schematically illustrate a user interface for
further visualizing and manipulating captured brain circulation
information, which includes additional, user-selectable options
625. FIG. 6A illustrates additional information pertaining to a
user-selected vessel 590, including a representation of real-time
pulsing of the vessel 590. The animation of the real-time
progressing wavefronts 630 represents the pressure, displacement,
and/or energy density waves propagating from the blood vessel over
time. Pulse wavefronts refer to the forward edge of a contiguous
fluidic mass. For example, a progressing, continuous train of
transverse wavefronts 630 can be shown, the transverse wavefronts
spatially evolving through the blood vessel wall and/or through
surrounding tissue fluid over each pulse cycle. The spatial
evolution of progressing transverse wavefronts can be represented
to spread and decay via outward motion from the vessel. Pulse
wavetrains, referring to more than one contiguous fluidic mass,
briefly expand a vessel wall during the transit of blood, and the
expansion pushes into extracellular fluid (ECF) and cells. This
expansion transports energy into the surrounding fluid and relates
to the delivery of nutrients which cross the blood-brain barrier.
An indicator 620, such as a battery, can represent to the user in a
visually and easily-comprehensible manner the assessed energy
delivery of the pulse wavetrains propagating from a vessel wall.
Additional options 625 can include a crawling feature 627 which
permits the user to see a slow-motion view of the pulse wavetrains
at, for example, half or quarter speeds, so that the user can
better see the inter-relationship between pulse and energy
delivery. Additional options 625 can also include selections for a
go-back option 626, a freeze-frame option 628, and an option for
viewing disparate aspects of the cardiovascular cycle together 629.
Other variables, such as the radial torqueing force of blood
against a vessel wall can also be changed in a "what-if" function
by the user.
[0140] In comparison with FIG. 6A, FIG. 6B schematically
illustrates the display of a subject having reduced pulse
wavefronts 630', representing poorer brain circulatory function.
For example, the pulse wavefront 630' is smaller in amplitude and
spreads more slowly over time. An indicator 620', such as a
battery, can also represent to the user reduced energy
delivery.
[0141] Additional representations of circulation are shown in FIG.
6C with oxygen barbells 635 representing sufficient oxygen
delivery. The oxygen barbells 635 can bob with represented
wavefronts. Additionally, several capillaries 640 are shown to
demonstrate a location at which oxygen gas molecules are actually
unloaded, as opposed to their traveling origins as plasma and each
HbO molecule is propelled through the vessel. All vessels pulse,
however capillaries pulse irregularly. In health, O.sub.2 oxygen
delivery is relative to O.sub.2 oxygen concentration in proximate
extracellular fluid and tissue, beyond capillary delivery of
oxygen. Oxygen concentration in surrounding fluid and/or tissue may
be calculated by pH, or by aerobic versus anaerobic pathway
assessments. An oxygen level indicator 645 can be displayed, which
can further represent the overall sufficiency of oxygen delivery to
a regional area near the selected blood vessel. For some users, it
may be important to show both deoxygenated hemoglobin and
oxygenated hemoglobin in cycle time.
[0142] FIGS. 7A-7B schematically illustrate a user interface in
which related but disparate anatomy are represented in the same
display. Option 710 is shown to be selected, which represents to
the user that features of the face and heart are shown together on
the display screen. Heart 715 is animated to pulse based upon
real-time information acquired from the subject or upon prior cycle
data obtained from the subject. Additionally, an artery 735 and a
capillary 745 are shown and display animated representations of
pulse wavefronts 730 and nutrient delivery arrows 760. Pulse
wavefronts 740 represent the blood rotationally spinning in a
spiral within artery 735. A deformed red blood cell 755 is depicted
squeezing through the capillary 745 with its embedded oxygen (HbO)
yet to be drawn down. A spent red blood cell 750 having a typical
biconcave shape is depicted, shown to be relatively depleted of
oxygen due to earlier O.sub.2 gradient drawdown in the tissue by
which the red blood cell 750 passed. This user interface provides
educational information, showing ejection from the heart and
nutrient delivery in the brain on the same screen. The heart,
artery, and capillary can be animated to correspond to each other
in real-time. For example, the pulsations of the heart precede the
pulse wavefronts 730 of the artery 735.
[0143] Touch actions within the user interface can allow the user
to see how his or her nutrient-in and waste-out systems relate and
depend upon each other. FIG. 7B depicts some cardiovascular
components and downstream components in abstract. During a first
phase, a heart 715 is initially shown in systole, during which
time, less blood 737 remains in the vessel 735 and nutrient
delivery arrows 760' are shown to be at a minimum. During a second
phase following systole, and after a period of time where blood has
reached the capillaries, nutrient delivery arrows 760 are shown to
increase. Additionally, a representation of a red blood cell 755 is
shown to travel through a capillary 745, with a precapillary
sphincter 765 in an open position. During the period of time after
a subject's mitral valve closes, but before the aortic valve opens,
concentric layers of blood can progressively counter-spin in a
conductive pattern with the rotational compression of blood
inducing contraction of the ventricle. The first phase, showing the
heart 715, vessel 735 and nutrient delivery 760' in cyclic
correspondence, shows the user that, during systole, a vessel has
less blood, which is travelling at a slow rotational/forward pace,
as a pulse wavefront has not yet occurred. The second phase shows
cyclic correspondence of the vessel 735, capillaries 745, and
nutrient delivery 760 during a pulse wavefront. Arrows 740
represent the rotational layers of spinning blood in the vessel
735. More rotations of blood relate to more energy delivered. The
heart and vasculature inter-animate at one time, to demonstrate
their relation and dependence on one another.
[0144] Touch actions can be available from the objects representing
the heart and vasculature. Examples of user input and corresponding
results are provided in Table 2.
TABLE-US-00002 TABLE 2 Touch actions by user and examples of
corresponding displays. Pinch Expand/Pinch Double Tap Swipe
Parallel to Normal to Precapillary Axial to Expand/Pinch User
Action vessel axis vessel axis sphincter nutrient flow Through
tissue Response Show "squeezing" Next class of vessel Show +5% Show
next stage: Increase "wash of vessel so (Vessel classes: tissue
oxygen Co2 efflux out" animation of less fluid can artery,
arteriole, usage, pcapO2 nutrients as they get through at
capillary, venule, and RBCs in are utilized/ a time, depicting and
vein) therefore increase slower velocity diffusion rate of
fluid
[0145] User interfaces for displaying transport aspects of venous
and cerebrospinal fluid are shown in FIGS. 8A-8C. By selecting the
pulsing surround 562 (FIG. 5B), the user may invoke displays and
animations pertaining to these other fluid compartments of the
brain: venous and CSF. CSF flow is fundamental to nourishing brain
tissue and removing toxic metabolic wastes. Together with blood
flow supplying the cerebral brain, CSF flow contributes to
intracranial pressure (ICP). CSF flow is subject to cycling
gradients of pressures, as described above with respect to blood
flow through vessels. Elevated intracranial pressure can lead to
increased cerebral perfusion pressure (CPP) and impaired filtration
from brain tissue and impaired nutrient uptake. Such impaired
function could lead to stroke, or could ensue as hydrocephalus.
Ageing, head injury and other factors can elevate ICP.
[0146] Because brain tissue is generally soft and pliable, in order
to metabolically absorb nutrients and eliminate waste via
surrounding flow, cerebral CSF flow and ICP are important factors.
CSF's slow, rhythmic flow pulsations help cause rippling of O2 gas
and molecules/ions towards tissue, and cause harmful byproducts,
such as CO2 gas, lactic acid, and acetic acid, to move away.
Although daily CSF production contributes to ICP, in healthy
individuals, the more rapid arterial flow pulsations influence the
volumetric ebb and flow against soft tissue of the
fairly-constrained bony cranial space. The only pathways out of
shielded cranial space due to incoming arterial/CSF pressure
gradients is via venous outflow and CSF outflow routes. Therefore,
arterial, ICP and venous circulatory functions influence one
another and the monitoring of CSF flow is also useful, in addition
to the monitoring of vascular blood flow.
[0147] As shown in FIG. 8A, a user interface for monitoring venous
flow and CSF aspects may appear in which facial vessels can
disappear while internal cerebral-related vessels manifest. Visual
landmarks, such as nose and eye placement may show. Superior
sagittal sinus anatomy 810 is depicted with upward flow. The
internal depth of the anatomy 810 may be represented with less
precise edging. CSF movement may be shown from an upper nasal
cavity via the cribriform plate or via the eye sockets, for example
the optic canal that runs alongside the orbital nerve. Venous fluid
flow can be shown in the sagittal sinus cavity and jugular veins.
Arterial pulsing can be shown in the carotid arteries.
[0148] As shown in FIG. 8B, if a user 895 touches a region of
interest 890, such as anatomy 810, the display can switch to
representing driving fluidic compartments.
[0149] As shown in FIG. 8C, a deformable balloon or bob 850
construct appears superimposed over the flowing region of interest
890, such as the superior sagittal sinus, and represents
pressure/volume imputed in this aspect of such a compartment,
whether a venous, CSF or arterial compartment. CSF outflow 860 via
the nasal cavity can also be represented. CSF fluxes at its own
rate and some splits to merge into venous outflow.
[0150] User interfaces for displaying representations of electrical
brain activity are shown in FIGS. 9A-9D. The selection of "Brain"
mode 535 (FIG. 5A) can invoke displays relating to the brain's
electrical activity. After selection, an icon 915 having a
lightning bolt, or other image, may appear to indicate to the user
that he or she is viewing the electrical activity mode, along with
other stage icons. Synapses are mapped and represented as dots 910.
The dots can represent the electrical activity of a relative area,
rather than single neurons. The dots can show in different
intensities and appear and fade in real time. The dots can show the
net increase and decrease per vascular cycle, or per time period,
or in real-time as images are continually captured of the subject's
anatomy.
[0151] As shown in FIG. 9B, the dots 910 can be actionable by a
finger-swipe to invoke a next stage. FIG. 9C illustrates the
overlay of two stages of Brain modes and includes an overlay of
dots 910 with an animated wave 920 representing the rippling or
flux of oxygen into the fluid and tissues of the brain. The display
may show the effective combination of healthy O2 delivery with a
healthy pH operating environment, as both are needed for neural
functioning. The combination of pH-O2 rippling can be cyclically
represented in visual waves having an amplitude and timing that is
synchronized with blood pulsations. The concentration of O2 and
acidity of the brain is likely to vary over a cycle duration and
can be represented as a gradient or gradient overlay.
[0152] If a subject has poor nutrient delivery, a slow oxygen wave
920' may appear with an alert flag 925. The colors of the display
can clearly denote any problem with pH-O2 rippling in regions of
risk. Regions of risk may be intermittent or time-cycle based, but
may be presented as static for ease of user comprehension.
Additionally, upon selection of the alert, the user may receive
options to view further specifics, to check again at a later
time/interval, automatically invoke the device at a later time,
and/or to send the information to a medical professional.
[0153] Further specifics of pH, oxygen rippling, and energy can be
displayed in details and represented with easily-comprehensible
figures as shown in FIG. 10, such as thermometer-type icons or
battery-type icons. In the detailed mode, pH 930, oxygen 935, and
energy 940 indicators are represented separately and may be
animated to show real-time changes.
[0154] An alternate user interface for representing brain health in
terms of electrical activity is shown in FIGS. 11A-11D. A
representation having a circuit 1105 can be displayed to the user.
The circuit may have a device-level breakdown, for example,
resistor-inductor-capacitor (RLC) representation, or it may have a
high-level representation showing time-coupled, amplitude-dependent
(wavelike) circuit equivalence. Spectroscopy can be used to compute
net charge activity, Q, and can be represented by dots 1110. In
turn, circuit 1105 may represent current, I, according to the
equation:
I=.DELTA.Q/time
[0155] Cycle time information may be displayed and may be
user-selectable through cycle time slider 1115. A showcased or
focused display of a circuit equivalence 1105 can be displayed
along with a miniature summary 1120 of what the user saw or likely
processed.
[0156] As shown in FIG. 11C, touch-activation by the user of
circuit 1105 can prompt a spin-pointer 1125 selection arising in
the middle of the circuit, with additional options. Alternatively,
or in addition to touch-activation, the user can pinch circuit
1105, as shown in FIG. 11D, to unveil resistance equivalence for
the circuit (not shown). The user can then adjust the resistance
(R) values to see the impedance effects. Resistance values may
correspond to stiffness of vessel walls and/or propagation delays.
Visualizing the effects of resistance on brain function can help
users visualize and understand how they may improve brain health
through, for example, increases in metabolism.
[0157] Examples of spin-pointer selection are shown in FIG. 12,
including representations for nutrient delivery 1205, energy 1210,
mental attention 1215, and semantic ability 1220. A user selection
of nutrient delivery 1205 can prompt, for example, detailed
information pertaining to nutrient input, CO2 waste output, and the
importance of H2O sufficiency. This information can help users
better comprehend, for example, their calcium intake and their
necessary cardiovascular/CSF flow in order to eliminate wastes.
Selection of energy 1210 can prompt, for example, additional
information on how the cardiovascular system transfers energy into
the brain and how circulatory function relates to brain
functioning. Energy information can include: educational
information regarding system inter-relationship, likely trends over
long periods of time, translation of newly forming circuit
equivalents into changes in energy storage, and hypothetical energy
deletion as it relates to loss of circuit maintenance in time.
[0158] Selection of mental attention 1215 can prompt information on
attention capabilities. How the brain selects from amongst many
visual stimuli, where to pay visual attention via select
amplification, and what to not pay attention to can be included in
this information. Selection of Semantic 1220 can prompt information
on word processing. Other features relating to nutrient delivery
1205 and energy 1210 can provide additional information for the
user.
[0159] Example menu items that can be activated from
user-selectable options 625 or other touch controls, such as
pinching, swiping, zooming are shown in Table 3. Alternatively, the
device may be voice-enabled, and users may interface with the
device through voice-control.
TABLE-US-00003 TABLE 3 Menu Items Version Risky Regions Compare
Rhythms 1 Show (zoom) on Ideal average Decompose high risk feed
(across all vascular vs locales and/or users or across respiratory
blockages age/gender) vs CSF Present "what-ifs": frequencies/ For
example, amplitudes slowing effect Present "what ifs": on cyclic
cycle Increase and tidal hemoglobin % volume after 1 uptake by say
1% min deep Increase toxic breathing, or waste % removal hastening
(CO2, lactic acid) effect after by 1% 20 mins brief exercise
Version Recalling It Compare More 2 Test My Strengths Ideal average
Flag if correlation (incremental (across all with heart attack/
charge levels, users or across stroke/Alzheimer's burst rate, use
age/gender) disease working memory) MyTachometer: rpm Ideal average
Burst "density" (across all (region per users or across cycle time)
e.g age/gender) blinking stars shows degree differentiation Test My
Speeds Ideal average Show baseline (across all energy/cycle; users
or across Prompt to age/gender) forward data for research/medical
purposes 3 Cycling through Mean across Patterning pyramidal-cell
age/gender response to type tests: input by age/ semantic, working
education memory Patterning response Versus past Fueling (such as
to test input; self-history ATP or glucose) classify verbal vs
(most recent math, or executive reading/next functioning, or
am/day/mo/yr) pediatrics Typical energy Buddy Signaling (e.g.
consumed when (designate email glutamate or actively storing
address of CA + 2) a "test" another person also using the
application): brain "racing" Cumulative energy Ideal average My
BrainPower: stored there via (across all users cerebral kinetic app
over time or across age/ energy (KE) or gender) KE density 4
Contrast metrics Racing/eval Projecting next via posture (i.e.
against a period's forehead below designated expert educational
step heart) pattern: by response to education (e.g. input; compare
SAT prep verbal/ actual/forecast math), by field .DELTA. pH via
(e.g. real-time bicarbonate trading), by buffering situational
safety system: wave (school-based) amplitudes (& "Health
circles" frequencies for w/multiple buddies rate of response) or
fitness partners Using relevant average, age forward a decade
[0160] FIG. 13 illustrates a computer network 110 or similar
digital processing environment in which the present invention may
be implemented. Mobile device or computer 50 and server computer(s)
60 provide processing, storage, and input/output devices executing
application programs and the like. Mobile device or computer 50 can
also be linked through communications network 70 to other computing
devices, including other client devices/processes 50 and server
computer(s) 60. Communications network 70 can be part of a remote
access network, a global network (e.g., the Internet), a worldwide
collection of computers, Local area or Wide area networks, and
gateways that currently use respective protocols (TCP/IP,
Bluetooth, etc.) to communicate with one another. Other electronic
device/computer network architectures are suitable.
[0161] FIG. 14 is a diagram of the internal structure of a computer
(e.g., mobile device/computer 50 or server computers 60). Mobile
device or computer 50 contains system bus 79, where a bus is a set
of hardware lines used for data transfer among the components of a
computer or processing system. Bus 79 is essentially a shared
conduit that connects different elements of a computer system
(e.g., processor, disk storage, memory, input/output ports, network
ports, etc.) that enables the transfer of information between the
elements. Attached to system bus 79 is I/O device interface 82 for
connecting various input and output devices (e.g., keyboard,
microphone, displays, cameras, spectroscopy devices, wearable aids,
speakers, etc.) to the computer 50, 60. Network interface 86 allows
the computer to connect to various other devices attached to a
network (e.g., network 70 of FIG. 13). Memory 90 provides volatile
storage for computer software instructions 92 and data 94 used to
implement an embodiment of the present invention (e.g., measurement
module/submodules, comparator, assessment module/submodules,
probability engine including evaluator and display/reporter module,
and supporting code detailed above). Disk storage 95 provides
non-volatile storage for computer software instructions 92 and data
94 used to implement an embodiment of the present invention.
Central processor unit 84 is also attached to system bus 79 and
provides for the execution of computer instructions.
[0162] In one embodiment, the processor routines 92 and data 94 are
a computer program product (generally referenced 92), including a
computer readable medium (e.g., a removable storage medium such as
one or more DVD-ROM's, CD-ROM's, diskettes, tapes, etc.) that
provides at least a portion of the software instructions for the
invention system. Computer program product 92 can be installed by
any suitable software installation procedure, as is well known in
the art. In another embodiment, at least a portion of the software
instructions may also be downloaded over a cable, communication
and/or wireless connection. In other embodiments, the invention
programs are a computer program propagated signal product embodied
on a propagated signal on a propagation medium (e.g., a radio wave,
an infrared wave, a laser wave, a sound wave, or an electrical wave
propagated over a global network such as the Internet, or other
network(s)). Such carrier medium or signals provide at least a
portion of the software instructions for the present invention
routines/program 92.
[0163] In alternate embodiments, the propagated signal is an analog
carrier wave or digital signal carried on the propagated medium.
For example, the propagated signal may be a digitized signal
propagated over a global network (e.g., the Internet), a
telecommunications network, or other network. In one embodiment,
the propagated signal is a signal that is transmitted over the
propagation medium over a period of time, such as the instructions
for a software application sent in packets over a network over a
period of milliseconds, seconds, minutes, or longer. In another
embodiment, the computer readable medium of computer program
product 92 is a propagation medium that the computer system 50 may
receive and read, such as by receiving the propagation medium and
identifying a propagated signal embodied in the propagation medium,
as described above for computer program propagated signal
product.
[0164] Generally speaking, the term "carrier medium" or transient
carrier encompasses the foregoing transient signals, propagated
signals, propagated medium, storage medium and the like.
[0165] The teachings of all patents, published applications and
references cited herein are incorporated by reference in their
entirety.
[0166] While this invention has been particularly shown and
described with references to example embodiments thereof, it will
be understood by those skilled in the art that various changes in
form and details may be made therein without departing from the
scope of the invention encompassed by the appended claims.
[0167] The foregoing written specification is considered to be
sufficient to enable one skilled in the art to practice the
invention. Various modifications of the invention in addition to
those shown and described herein will become apparent to those
skilled in the art from the foregoing description and fall within
the scope of the appended claims. The advantages and objects of the
invention are not necessarily encompassed by each embodiment of the
invention. Those skilled in the art will recognize, or be able to
ascertain using no more than routine experimentation, many
equivalents to the specific embodiments described herein, which
fall within the scope of the claims. The scope of the present
invention is not to be limited by or to embodiments or examples
described above.
[0168] Section headings used herein are not to be construed as
limiting in any way. It is expressly contemplated that subject
matter presented under any section heading may be applicable to any
aspect or embodiment described herein.
[0169] Embodiments or aspects herein may be directed to any agent,
composition, article, kit, and/or method described herein. It is
contemplated that any one or more embodiments or aspects can be
freely combined with any one or more other embodiments or aspects
whenever appropriate. For example, any combination of two or more
agents, compositions, articles, kits, and/or methods that are not
mutually inconsistent, is provided.
[0170] Articles such as "a", "an", "the" and the like, may mean one
or more than one unless indicated to the contrary or otherwise
evident from the context.
[0171] The phrase "and/or" as used herein in the specification and
in the claims, should be understood to mean "either or both" of the
elements so conjoined. Multiple elements listed with "and/or"
should be construed in the same fashion, i.e., "one or more" of the
elements so conjoined. Other elements may optionally be present
other than the elements specifically identified by the "and/or"
clause. As used herein in the specification and in the claims, "or"
should be understood to have the same meaning as "and/or" as
defined above. For example, when used in a list of elements, "or"
or "and/or" shall be interpreted as being inclusive, i.e., the
inclusion of at least one, but optionally more than one, of list of
elements, and, optionally, additional unlisted elements. Only terms
clearly indicative to the contrary, such as "only one of" or
"exactly one of" will refer to the inclusion of exactly one element
of a number or list of elements. Thus claims that include "or"
between one or more members of a group are considered satisfied if
one, more than one, or all of the group members are present,
employed in, or otherwise relevant to a given product or process
unless indicated to the contrary. Embodiments are provided in which
exactly one member of the group is present, employed in, or
otherwise relevant to a given product or process.
[0172] Embodiments are provided in which more than one, or all of
the group members are present, employed in or otherwise relevant to
a given product or process. Any one or more claims may be amended
to explicitly exclude any embodiment, aspect, feature, element, or
characteristic, or any combination thereof. Any one or more claims
may be amended to exclude any agent, composition, amount, dose,
administration route, cell type, target, cellular marker, antigen,
targeting moiety, or combination thereof.
[0173] Embodiments in which any one or more limitations, elements,
clauses, descriptive terms, etc., of any claim (or relevant
description from elsewhere in the specification) is introduced into
another claim are provided. For example, a claim that is dependent
on another claim may be modified to include one or more elements or
limitations found in any other claim that is dependent on the same
base claim. It is expressly contemplated that any amendment to a
genus or generic claim may be applied to any species of the genus
or any species claim that incorporates or depends on the generic
claim.
[0174] Where a claim recites a composition, methods of using the
composition as disclosed herein are provided, and methods of making
the composition according to any of the methods of making disclosed
herein are provided. Where a claim recites a method, a composition
for performing the method is provided. Where elements are presented
as lists or groups, each subgroup is also disclosed. It should also
be understood that, in general, where embodiments or aspects is/are
referred to herein as comprising particular element(s), feature(s),
agent(s), substance(s), step(s), etc., (or combinations thereof),
certain embodiments or aspects may consist of, or consist
essentially of, such element(s), feature(s), agent(s),
substance(s), step(s), etc. (or combinations thereof). It should
also be understood that, unless clearly indicated to the contrary,
in any methods claimed herein that include more than one step or
act, the order of the steps or acts of the method is not
necessarily limited to the order in which the steps or acts of the
method are recited. Any method of treatment may comprise a step of
providing a subject in need of such treatment, e.g., a subject
having a disease for which such treatment is warranted. Any method
of treatment may comprise a step of diagnosing a subject as being
in need of such treatment, e.g., diagnosing a subject as having a
disease for which such treatment is warranted.
[0175] Where ranges are given herein, embodiments in which the
endpoints are included, embodiments in which both endpoints are
excluded, and embodiments in which one endpoint is included and the
other is excluded, are provided. It should be assumed that both
endpoints are included unless indicated otherwise. Unless otherwise
indicated or otherwise evident from the context and understanding
of one of ordinary skill in the art, values that are expressed as
ranges can assume any specific value or subrange within the stated
ranges in various embodiments, to the tenth of the unit of the
lower limit of the range, unless the context clearly dictates
otherwise. "About" in reference to a numerical value generally
refers to a range of values that fall within .+-.10%, in some
embodiments .+-.5%, in some embodiments .+-.1%, in some embodiments
.+-.0.5% of the value unless otherwise stated or otherwise evident
from the context. In any embodiment in which a numerical value is
prefaced by "about", an embodiment in which the exact value is
recited is provided. Where an embodiment in which a numerical value
is not prefaced by "about" is provided, an embodiment in which the
value is prefaced by "about" is also provided. Where a range is
preceded by "about", embodiments are provided in which "about"
applies to the lower limit and to the upper limit of the range or
to either the lower or the upper limit, unless the context clearly
dictates otherwise. Where a phrase such as "at least", "up to", "no
more than", or similar phrases, precedes a series of numbers, it is
to be understood that the phrase applies to each number in the list
in various embodiments (it being understood that, depending on the
context, 100% of a value, e.g., a value expressed as a percentage,
may be an upper limit), unless the context clearly dictates
otherwise. For example, "at least 1, 2, or 3" should be understood
to mean "at least 1, at least 2, or at least 3" in various
embodiments. It will also be understood that any and all reasonable
lower limits and upper limits are expressly contemplated.
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