U.S. patent application number 15/945502 was filed with the patent office on 2018-10-11 for magnetic apparatus.
The applicant listed for this patent is Howard Hughes Medical Institute. Invention is credited to Mladen Barbic, Stephen Dodd, Alan Koretsky, Herman Douglas Morris.
Application Number | 20180292478 15/945502 |
Document ID | / |
Family ID | 63710862 |
Filed Date | 2018-10-11 |
United States Patent
Application |
20180292478 |
Kind Code |
A1 |
Barbic; Mladen ; et
al. |
October 11, 2018 |
MAGNETIC APPARATUS
Abstract
An imaging apparatus for imaging a sample includes a magnetic
apparatus that defines a sample volume that is large enough to
accommodate the sample to be imaged, and one or more magnetically
manipulatable materials within the sample. The magnetic apparatus
includes a magnet that is configured to create a magnetic field
having a magnitude B in the sample Each magnetically manipulatable
material is a material that exhibits a transition between a first
magnetic state and a second magnetic state in response to a change
in a property associated with the sample while the magnetic field
having the magnitude B is maintained in the sample.
Inventors: |
Barbic; Mladen; (Sterling,
VA) ; Dodd; Stephen; (Rockville, MD) ; Morris;
Herman Douglas; (Germantown, MD) ; Koretsky;
Alan; (Bethesda, MD) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Howard Hughes Medical Institute |
Chevy Chase |
MD |
US |
|
|
Family ID: |
63710862 |
Appl. No.: |
15/945502 |
Filed: |
April 4, 2018 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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62482072 |
Apr 5, 2017 |
|
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|
62632201 |
Feb 19, 2018 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 49/06 20130101;
G01R 33/5601 20130101; G01R 33/281 20130101; A61N 2/00 20130101;
G01R 33/31 20130101; G01R 33/3815 20130101; A61B 5/0515 20130101;
A61B 5/055 20130101; A61B 5/01 20130101 |
International
Class: |
G01R 33/31 20060101
G01R033/31; G01R 33/3815 20060101 G01R033/3815; G01R 33/28 20060101
G01R033/28; A61B 5/055 20060101 A61B005/055; A61K 49/06 20060101
A61K049/06 |
Claims
1. An imaging apparatus for imaging a sample, the apparatus
comprising: a magnetic apparatus that defines a sample volume that
is large enough to accommodate the sample to be imaged, the
magnetic apparatus including a magnet that is configured to create
a magnetic field having a magnitude B in the sample; and one or
more magnetically manipulatable materials within the sample, each
magnetically manipulatable material being a material that exhibits
a transition between a first magnetic state and a second magnetic
state in response to a change in a property associated with the
sample while the magnetic field having the magnitude B is
maintained in the sample.
2. The imaging apparatus of claim 1, further comprising an energy
supply connected to the magnet, wherein the magnet includes
electrically conductive wire coils through which current from the
energy supply is passed, wherein the energy supply provides a DC
current supplied to the wire coils.
3. The imaging apparatus of claim 2, wherein the magnet is a
superconducting magnet.
4. The imaging apparatus of claim 1, wherein the magnetic field
magnitude B is greater than 0.5 Tesla or in a range of 1-20
Tesla.
5. The imaging apparatus of claim 1, wherein the first magnetic
state is an antiferromagnetic state or a paramagnetic state, and
the second magnetic state is a ferromagnetic state or a
ferrimagnetic state.
6. The imaging apparatus of claim 1, wherein the property
associated with the sample is a temperature, and the transition
occurs in response to a change in temperature less than 20 K.
7. The imaging apparatus of claim 1, further comprising a sample
property scanning system configured to change the property of the
sample while the magnetic field having magnitude B is maintained in
the sample.
8. The imaging apparatus of claim 1, wherein the property
associated with the sample is a magnetic field, and the transition
occurs in response to a change in a magnitude of a magnetic field
that is substantially smaller than the magnitude B.
9. The imaging apparatus of claim 1, wherein the magnetic apparatus
is a magnetic resonance imaging apparatus.
10. The imaging apparatus of claim 1, wherein the magnetically
manipulatable material is a magnetocaloric material.
11. The imaging apparatus of claim 1, wherein the magnetically
manipulatable material is a material selected from the group
consisting of iron-rhodium, alloys of iron-rhodium, alloys of
manganese arsenide, Heusler alloys, and alloys of
manganese-iron.
12. The imaging apparatus of claim 1, wherein the sample is a
living organism and the sample is held at a physiological
temperature to maintain the organism in a living state.
13. The imaging apparatus of claim 1, further comprising a detector
that detects a signal produced as a result of the interaction
between the magnetic field and the sample.
14. The imaging apparatus of claim 13, further comprising a control
system connected to the magnetic apparatus, wherein the control
system is configured to: receive data output from the detector, the
output relating to the detected signal, analyze the received data,
and estimate the sample property based on the analysis.
15. The imaging apparatus of claim 1, wherein each magnetically
manipulatable material is in the form of a plurality of
spatially-separated particles, wherein the particles are dispersed
throughout at least one region of interest within the sample.
16. The imaging apparatus of claim 15, wherein the size of the
particles is on the order of the size of cells within a sample that
is a living organism.
17. The imaging apparatus of claim 1, wherein the magnetically
manipulatable material remains magnetically unsaturated while the
magnetic field having the magnitude B exists in the sample.
18. The imaging apparatus of claim 1, wherein the one or more
magnetically manipulatable materials comprises a plurality of
magnetically manipulatable materials, with each magnetically
manipulatable material having a transition that occurs in response
to a distinct change in the property of the sample.
19. The imaging apparatus of claim 18, wherein: a first of the
magnetically manipulatable materials has a transition from the
first magnetic state to the second magnetic state that occurs in
response to an increase in the sample property; and a second of the
magnetically manipulatable materials has a transition from the
first magnetic state to the second magnetic state that occurs in
response to a decrease in the sample property.
20. The imaging apparatus of claim 18, wherein: a first of the
magnetically manipulatable materials has a transition from the
first magnetic state to the second magnetic state that occurs in
response to an increase in the sample property; and a second of the
magnetically manipulatable materials has a transition from the
second magnetic state to the first magnetic state that occurs in
response to an increase in the sample property.
21. The imaging apparatus of claim 18, wherein: a first of the
magnetically manipulatable materials has a transition between the
first magnetic state and the second magnetic state that occurs in
response to a change in a first sample property; and a second of
the magnetically manipulatable materials has a transition between
the first magnetic state and the second magnetic state that occurs
in response to a change in a second sample property that is
distinct from the first sample property.
22. The imaging apparatus of claim 1, wherein: the transition from
the first magnetic state to the second magnetic state occurs in a
first range of values of the property as the property is increased;
the transition from the second magnetic state to the first magnetic
state occurs in a second range of values of the property as the
property is decreased; and the first range of values is distinct
from the second range of values.
23. A method comprising: receiving a sample in a sample volume
defined by a magnetic apparatus; preparing at least one
magnetically manipulatable material within the sample; creating a
magnetic field having a magnitude B in the sample; changing a
property associated with the sample while maintaining the magnetic
field having the magnitude B in the sample; and detecting a
transition between a first magnetic state and a second magnetic
state of a magnetically manipulatable material in the sample in
response to the changing property associated with the sample.
24. The method of claim 23, wherein changing the property
associated with the sample comprises changing a temperature in the
sample in a range that is less than 20 K.
25. The method of claim 23, wherein changing the property
associated with the sample comprises changing a magnetic field in
the sample in a range that is substantially smaller than the
magnitude B.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional
Application No. 62/482,072, filed Apr. 5, 2017 and to U.S.
Provisional Application No. 62/632,201, filed Feb. 19, 2018, both
of which are incorporated herein by reference in their
entirety.
TECHNICAL FIELD
[0002] The disclosed subject matter relates to magnetic apparatuses
that employ magnetically manipulatable materials within a
sample.
BACKGROUND
[0003] Magnetic apparatuses can be used for imaging. For example, a
magnetic imaging apparatus such as a magnetic resonance imaging
(MM) apparatus uses magnetic fields to image or visualize internal
structures of samples such as a physiological or biological sample.
An MRI apparatus can use labels in the sample to help imaging.
SUMMARY
[0004] In some general aspects, an imaging apparatus is configured
to image a sample. The apparatus includes a magnetic apparatus that
defines a sample volume that is large enough to accommodate the
sample to be imaged, and one or more magnetically manipulatable
materials within the sample. The magnetic apparatus includes a
magnet that is configured to create a magnetic field having a
magnitude B in the sample. Each magnetically manipulatable material
is a material that exhibits a transition between a first magnetic
state and a second magnetic state in response to a change in a
property associated with the sample while the magnetic field having
the magnitude B is maintained in the sample.
[0005] Implementations can include one or more of the following
features. For example, the imaging apparatus can also include an
energy supply connected to the magnet. The magnet can include
electrically conductive wire coils through which current from the
energy supply is passed, and the energy supply can provide a DC
current supplied to the wire coils. The magnet can be a
superconducting magnet.
[0006] The magnetic field magnitude B can be greater than 0.5 Tesla
or in a range of 1-20 Tesla.
[0007] The first magnetic state can be an antiferromagnetic state
or a paramagnetic state, and the second magnetic state can be a
ferromagnetic state or a ferrimagnetic state.
[0008] The magnetically manipulatable material can exhibit the
transition while the temperature in the sample is between 270 and
370 K.
[0009] The property associated with the sample can be a
temperature, and the transition can occur in response to a change
in temperature less than 20 K.
[0010] The imaging apparatus can include a sample property scanning
system configured to change the property of the sample while the
magnetic field having magnitude B is maintained in the sample. The
sample property scanning system can include one or more of: a
temperature scanning system for changing a temperature of the
sample; and a magnetic scanning system for changing a magnetic
field of the sample. The temperature scanning system can include an
apparatus thermally connected to the sample. The thermally
connected apparatus can include an induction heater that operates
at either a medium frequency or a radio frequency range and
includes a controller, and a heat inductor.
[0011] The property associated with the sample can be a magnetic
field, and the transition can occur in response to a change in a
magnitude of a magnetic field that is substantially smaller than
the magnitude B.
[0012] The magnetic apparatus can be a magnetic resonance imaging
apparatus. The imaging apparatus can include one or more gradient
magnets configured to produce a variable magnetic field that has a
magnitude Y that is substantially smaller than the magnitude B; and
an electromagnetic source configured to produce a varying
electromagnetic field having a magnetic field magnitude that is
substantially smaller than the magnitude B.
[0013] The imaging apparatus can also include a delivery apparatus
configured to transport the magnetically manipulatable material
into the sample.
[0014] The magnetically manipulatable material can be a
magnetocaloric material. The magnetically manipulatable material
can be a material selected from the group consisting of
iron-rhodium, alloys of iron-rhodium, alloys of manganese arsenide,
Heusler alloys, and alloys of manganese-iron.
[0015] The sample can be a living organism and the sample can
therefore be held at a physiological temperature to maintain the
organism in a living state.
[0016] The imaging apparatus can include a detector that detects a
signal produced as a result of the interaction between the magnetic
field and the sample. The imaging apparatus can include a control
system connected to the magnetic apparatus. The control system can
be configured to: receive data output from the detector, the output
relating to the detected signal, analyze the received data, and
estimate the sample property based on the analysis. The imaging
apparatus can include a display. The control system can be
configured to create an image of the sample at the display based on
the analysis. The detector can detect the signal produced as a
result of the interaction between the magnetic field and the sample
by detecting a signal produced by tissue within the sample that is
in proximity of the magnetically manipulatable material. The signal
produced by tissue within the sample that is in proximity of the
magnetically manipulatable material can include electromagnetic
radiation generated from protons within the sample in proximity of
the magnetically manipulatable material.
[0017] Each magnetically manipulatable material can be in the form
of a plurality of spatially-separated particles. The particles can
be dispersed throughout at least one region of interest within the
sample. The size of the particles can be on the order of the size
of cells within a sample that is a living organism. The size of the
particles can be on the order of micrometers. Each particle can
have a microscopic size.
[0018] The magnetically manipulatable material can remain
magnetically unsaturated while the magnetic field having the
magnitude B exists in the sample.
[0019] The one or more magnetically manipulatable materials can
include a plurality of magnetically manipulatable materials, with
each magnetically manipulatable material having a transition that
occurs in response to a distinct change in the property of the
sample.
[0020] A first of the magnetically manipulatable materials can have
a transition from the first magnetic state to the second magnetic
state that occurs in response to an increase in the sample
property. And, a second of the magnetically manipulatable materials
can have a transition from the first magnetic state to the second
magnetic state that occurs in response to a decrease in the sample
property.
[0021] A first of the magnetically manipulatable materials can have
a transition from the first magnetic state to the second magnetic
state that occurs in response to an increase in the sample
property. And, a second of the magnetically manipulatable materials
can have a transition from the second magnetic state to the first
magnetic state that occurs in response to an increase in the sample
property.
[0022] A first of the magnetically manipulatable materials can have
a transition between the first magnetic state and the second
magnetic state that occurs in response to a change in a first
sample property. And, a second of the magnetically manipulatable
materials can have a transition between the first magnetic state
and the second magnetic state that occurs in response to a change
in a second sample property that is distinct from the first sample
property.
[0023] The transition from the first magnetic state to the second
magnetic state can occur in a first range of values of the property
as the property is increased. The transition from the second
magnetic state to the first magnetic state can occur in a second
range of values of the property as the property is decreased. The
first range of values is distinct from the second range of
values.
[0024] In other general aspects, a method includes: receiving a
sample in a sample volume defined by a magnetic apparatus;
preparing at least one magnetically manipulatable material within
the sample; creating a magnetic field having a magnitude B in the
sample; changing a property associated with the sample while
maintaining the magnetic field having the magnitude B in the
sample; and detecting a transition between a first magnetic state
and a second magnetic state of a magnetically manipulatable
material in the sample in response to the changing property
associated with the sample.
[0025] Implementations can include one or more of the following
features. For example, the method can include supplying energy to
the magnet in the form of a DC current.
[0026] The magnetic field of magnitude B can be greater than 0.5
Tesla or in a range of 1-20 Tesla.
[0027] The first magnetic state can be an antiferromagnetic state
or a paramagnetic state, and the second magnetic state can be a
ferromagnetic state or a ferrimagnetic state.
[0028] The property associated with the sample can be changed while
maintaining the temperature in the sample at a value between 270
and 370 K. The property associated with the sample can be changed
by changing a temperature in the sample in a range that is less
than 20 K. The property associated with the sample can be changes
by changing a magnetic field in the sample in a range that is
substantially smaller than the magnitude B.
[0029] The method can include: producing a variable magnetic field
that has a magnitude Y that is substantially smaller than the
magnitude B; and producing a varying electromagnetic field having a
magnetic field magnitude that is substantially smaller than the
magnitude B.
[0030] The at least one magnetically manipulatable material can be
prepared within the sample by transporting the magnetically
manipulatable material into the sample. The magnetically
manipulatable material can be transported into the sample by
dispersing the magnetically manipulatable material in the form of a
plurality of particles throughout at least one region of interest
within the sample.
[0031] The sample can be a living organism, and the method can also
include maintaining a temperature of the sample at a physiological
temperature to maintain the organism in a living state.
[0032] The method can include detecting a signal produced as a
result of the interaction between the magnetic field and the
sample. The method can include: receiving the detected signal
produced as a result of the interaction between the magnetic field
and the sample; analyzing the detected signal; and estimating the
sample property based on the analysis. The method can include
creating an image of the sample based on the analysis.
[0033] The signal produced as a result of the interaction between
the magnetic field and the sample can be detected by detecting a
signal produced by tissue within the sample that is in proximity of
the magnetically manipulatable material. The signal produced as a
result of the interaction between the magnetic field and the sample
can be detected by detecting electromagnetic radiation generated
from protons within the sample in proximity of the magnetically
manipulatable material.
[0034] The at least one magnetically manipulatable material can
include a plurality of magnetically manipulatable materials, with
each magnetically manipulatable material having a transition that
occurs in response to a distinct change in the property of the
sample.
[0035] The transition from the first magnetic state to the second
magnetic state can occur in a first range of values of the property
as the property is increased; the transition from the second
magnetic state to the first magnetic state can occur in a second
range of values of the property as the property is decreased; and
the first range of values is distinct from the second range of
values. The transition between the first magnetic state and the
second magnetic state of the magnetically manipulatable material in
the sample can be detected by: detecting the transition from the
first magnetic state to the second magnetic state as the property
is increased; detecting the transition from the first magnetic
state to the second magnetic state as the property is decreased;
detecting the transition from the second magnetic state to the
first magnetic state as the property is increased; or detecting the
transition from the second magnetic state to the first magnetic
state as the property is decreased.
[0036] In other general aspects, an imaging apparatus includes: a
magnetic apparatus that defines a sample volume that is large
enough to accommodate a sample to be imaged. The magnetic apparatus
includes a magnet that is configured to create a magnetic field
having a magnitude B in the sample. While the magnetic field having
a magnitude B is maintained in the sample, one or more magnetically
manipulatable materials within the sample transition between a
first magnetic state and a second magnetic state.
DESCRIPTION OF DRAWINGS
[0037] FIG. 1 is a block diagram of an apparatus including a
magnetic apparatus having a magnet and a magnetically manipulatable
structure embedded in a body of a sample in the magnet;
[0038] FIG. 2 is a block diagram of an implementation of the
apparatus of FIG. 1 in which the magnetically manipulatable
structure includes one or more magnetically manipulatable
materials, each magnetically manipulatable material being a
material that exhibits a transition between a first magnetic state
and a second magnetic state in response to a change in a property
associated with the sample;
[0039] FIG. 3A is a graph of a magnetic state M (or magnetic
moment) of an implementation of a magnetically manipulatable
material that can be in the magnetically manipulatable structure of
FIG. 2 versus the sample property, where the sample property is the
temperature T;
[0040] FIG. 3B is a graph of a magnetic state M (or magnetic
moment) of an implementation of a magnetically manipulatable
material that can be in the magnetically manipulatable structure of
FIG. 2 versus the sample property, where the sample property is the
temperature T;
[0041] FIG. 4 is a graph of a magnetic state M (or magnetic moment)
of an implementation of a magnetically manipulatable material that
can be in the magnetically manipulatable structure of FIG. 2 versus
the sample property, where the sample property is the magnetic
field within the sample;
[0042] FIG. 5A is a graph of a magnetic state M (or magnetic
moment) of an implementation of a magnetically manipulatable
material versus the sample property, where the sample property is
the magnetic field within the sample;
[0043] FIG. 5B is a graph of a magnetic state M (or magnetic
moment) of an implementation of a magnetically manipulatable
material versus the sample property, where the sample property is
the temperature within the sample;
[0044] FIG. 6A is a schematic representation of a sample in which
the magnetically manipulatable structure includes a plurality of
different magnetically manipulatable materials;
[0045] FIG. 6B is a graph of a magnetic state M (or magnetic
moment) of the two magnetically manipulatable materials of FIG. 6A
within the sample versus the sample property, where the sample
property is the magnetic field within the sample;
[0046] FIG. 7A is a graph showing an implementation of a
magnetically manipulatable material that transitions from a
magnetic to a non-magnetic state with a rise in temperature;
[0047] FIG. 7B is a graph showing an implementation of a
magnetically manipulatable material that transitions from a
non-magnetic to a magnetic state with a rise in temperature;
[0048] FIG. 8 is a graph of a magnetic state M of the first and the
second magnetically manipulatable materials of FIGS. 7A and 7B
within the sample versus temperature;
[0049] FIG. 9 is a block diagram of an implementation of the
apparatus of FIG. 1 in which the magnetically manipulatable
structure is a magnetocaloric actuator that is thermally coupled
with a thermally-sensitive biological construct within the
sample;
[0050] FIGS. 10A and 10B are schematic illustrations of an
implementation in which the thermally-sensitive biological
construct of FIG. 9 is an ion channel positioned along a cellular
structure of the sample, the magnetocaloric actuator includes a
plurality of magnetically manipulatable materials near the ion
channel; and the ion channel has a closed status (FIG. 10A) or an
open status (FIG. 10B);
[0051] FIG. 11 is a schematic illustration of an implementation of
a sample that includes a plurality of thermally-sensitive
biological constructs and a magnetocaloric actuator associated with
each of these biological constructs;
[0052] FIG. 12 is a schematic illustration of an implementation of
a single magnetocaloric actuator having different magnetically
manipulatable materials that are mixed together (but do not
interact with each other);
[0053] FIG. 13 is a schematic illustration of an implementation of
a test apparatus for demonstrating the feasibility of using
magnetocaloric materials as thermal actuators of
temperature-sensitive biological constructs in genetically-modified
cells while in a DC magnetic field;
[0054] FIG. 14A is a graph of a measurement of the magnetic moment
of a 99% purity FeRh structure as a function of temperature in
different bias DC magnetic fields;
[0055] FIG. 14B is a graph of a measurement of the magnetic moment
of a 99.9% purity FeRh structure as a function of temperature in
different bias DC magnetic fields;
[0056] FIG. 15A is a graph of a measurement of the magnetic moment
of a 99% purity FeRh structure as a function of varying magnetic
field at constant temperature;
[0057] FIG. 15B is a graph of a measurement of the magnetic moment
of a 99.9% purity FeRh structure as a function of varying magnetic
field at constant temperature;
[0058] FIG. 16 is a block diagram of an implementation of a testing
apparatus to demonstrate operation of the apparatus of FIGS. 1, 2,
and 9 in which a disk of FeRh is embedded in agarose next to a
thermometer 1681;
[0059] FIGS. 17A-17F are representative gradient-echo images
showing the effect of the FeRh mm-scale disk of FIG. 16 on the
surrounding agarose as the temperature of the set-up is swept
through a physiologically relevant temperature range (10-55.degree.
C.) at a constant MM magnetic field of 4.7 Tesla;
[0060] FIG. 17G is a graph of a width of an image artifact (or MRI
signal) of FIGS. 17A-17F that is created by signal loss due to the
magnetic field gradients from the FeRh disk of FIG. 16 as a
function of the set-up temperature;
[0061] FIG. 18A is a graph of a magnetic moment of a magnetocaloric
material versus temperature, which shows a transition from a first
magnetic state to a second magnetic state, in which the center of
the first order magnetic phase transition of the magnetocaloric
material is at the physiological temperature of 37.degree. C.;
[0062] FIG. 18B is a graph of a magnetic moment of a magnetocaloric
material versus temperature, which shows a transition from a first
magnetic state to a second magnetic state, in which the center of
the first order magnetic phase transition of the magnetocaloric
material is greater than the physiological temperature of
37.degree. C.;
[0063] FIG. 18C is a graph of a magnetic moment of two
magnetocaloric materials that have phase transitions at two
different magnetic field values at the physiological
temperature;
[0064] FIG. 19A is a graph of a magnetic moment of first
magnetically manipulatable material versus temperature, in which
the magnetically manipulatable material is Fe--La--Si;
[0065] FIG. 19B is a graph of a magnetic moment of first
magnetically manipulatable material versus temperature, in which
the magnetically manipulatable material is 99% purity FeRh;
[0066] FIG. 20 is a flow chart of a procedure performed by the
apparatus of FIG. 2 for using the magnetic apparatus and the
magnetically manipulatable structure to control, alter, or operate
on the sample; and
[0067] FIG. 21 is a flow chart of a procedure performed by the
apparatus of FIG. 9 for actuating (for example, activating and
de-activating) a biological construct (which can be the
thermally-sensitive biological construct within the sample.
DETAILED DESCRIPTION
[0068] Referring to FIG. 1, an apparatus 100 is shown that uses a
magnetic apparatus 105 to perform one or more functions or
operations on a sample 115. The sample 115 is a three-dimensional
body. The sample 115 can be a biological or physiological organism
or tissue and can be alive. The magnetic apparatus 105 includes a
magnet 120 that defines a sample volume 110 that is large enough to
accommodate the sample 115. The magnet 120 is configured to create
a magnetic field having a magnitude B in the sample 115. The
apparatus 100 includes an energy supply 125 connected to the magnet
120 and a control system 140 connected to one or more components
(such as the energy supply 125 and the magnet 120) of the magnetic
apparatus 105.
[0069] The magnetic apparatus 105 includes a magnetically
manipulatable structure 135 embedded within the body of the sample
115. The magnetically manipulatable structure 135 is controlled by
at least the magnet 120 to affect the function of and operation of
the sample 115. The magnetically manipulatable structure 135
includes one or more magnetically manipulatable materials, which
can be magnetocaloric materials. The magnetocaloric material is a
material that exhibits a transition between a first magnetic state
and a second magnetic state in response to a change in a property
associated with the sample 115 while the magnetic field having the
magnitude B is maintained in the sample 115. This transition can be
used to affect the function of or operation of the sample 115.
Additionally, the magnetocaloric material experiences a temperature
change in response to a changing magnetic field and this
temperature change can be used to affect the function of or
operation of the sample 115. The magnetically manipulatable
material 135 has magnetic properties that can be changed and this
change can occur around the temperature of a living organism and
also in the presence of large DC magnetic fields of MRI
scanners.
[0070] While the magnetically manipulatable structure 135 is shown
as a monolithic structure in the sample 115 in FIG. 1, it is
possible for the magnetically manipulatable structure 135 to be a
diffuse or disconnected structure 135 within the sample 115. For
example, the structure 135 can include some materials in one region
of the sample 115 and other materials in another distinct and
separate region of the sample 115.
[0071] Magnetocaloric materials can have a sharp and tunable
transition of magnetization with respect to changes in an
environment in which the magnetocaloric material is placed. For
example, if the magnetocaloric material is within a sample (such as
the sample 115), then the magnetocaloric material has a sharp and
tunable transition of magnetization with respect to changes in one
or more properties of the sample when the sample is held at a
particular magnetic field. A sample property that can be changed is
the temperature or the magnetic field of the sample 115. If the
sample 115 is a biological sample, then it is held at a magnetic
field that is suitable for the biological sample, and also held at
temperatures that are suitable, for example, a typical
physiological (body) temperatures and fields of several Teslas (for
example, 1 to 20 Teslas). Thus, magnetocaloric materials can be
made to be sharply visible or invisible (switchable) in typical
magnetic resonance imaging (MRI) machines in response to small
changes in properties (for example, temperature or magnetic field)
associated with the sample. This makes magnetocaloric materials
suitable as sensors and/or labels in the sample. Moreover, the
location and properties of these magnetization transitions can be
widely tunable in magnetocaloric materials by various materials
science techniques of alloying, doping, annealing, for example,
thus making the MRI sensor and label design possibilities wide
ranging.
[0072] Magnetocaloric materials have magnetic properties that
provide a close match to the requirements for the design of high
contrast ratio switchable and tunable MM labels. More specifically,
careful examination of the magnetocaloric materials' magnetic
properties reveals that some of them have extremely sharp
first-order magnetic phase transitions at typical physiological
temperatures and in the presence of the large Tesla-scale magnetic
fields typical of MRI settings. Furthermore, these sharp
first-order magnetic phase transitions can have a positive or
negative slope of magnetization vs. temperature, making them even
stronger candidates as versatile materials for high differential
contrast switchable MRI labels. Finally, magnetocaloric materials
can be engineered and their magnetic properties fine-tuned through
materials science techniques such as doping, alloying, thermal
treatments and the like to optimize their response under
physiological and MM-appropriate conditions. As discussed below,
the basic magneto-physical and MM measurements on samples of
iron-rhodium (FeRh) are described in order to develop the case for
and demonstrate the use of such materials for high differential
contrast ratio MRI labels.
[0073] For example, the magnetocaloric material is a material
selected from the group consisting of iron-rhodium (FeRh), alloys
of iron-rhodium, alloys of manganese arsenide, Heusler alloys,
alloys of manganese-iron, alloys of lanthanum, iron, and silicon,
and gadolinium.
[0074] Accordingly, as discussed herein, magnetocaloric materials
can be used as tunable and switchable labels and sensors for MRI
applications. These magnetocaloric materials have sharp magnetic
phase transitions at typical physiological temperatures and in the
presence of the large DC magnetic field values associated with MM
machines. This means that they have a sharp change in magnetization
for a small change in temperature or magnetic field in the
experimental settings typical of MM machines, which makes them
uniquely suitable as MM contrast agents and sensors. A change of
magnetization of the magnetocaloric material can be detected in MM
by observing the effect this change in magnetization has on water
or biological tissue surrounding the material. Furthermore, the
magnetic properties of magnetocaloric materials can be tuned by
appropriate materials science technique of alloying, doping, and
temperature treatments, for example.
[0075] Magnetocaloric materials can be used as sensors of
temperature or magnetic field in typical MRI settings of
physiological temperature and large bias magnetic fields of 1-20
Tesla. Magnetocaloric materials can be used as switchable MM labels
in typical MM settings of physiological temperature and large bias
magnetic fields of 1-20 Tesla.
[0076] Magnetocaloric materials can be switched on or off in
typical MM settings of physiological temperature and large bias
magnetic fields of 1-20 Tesla by either a change in magnetic field
or a change in temperature or a combination of both. Magnetocaloric
materials can have positive or negative slope of magnetization vs.
temperature, which means that the labels can be made to be positive
labels (can turn on with rise in temperature) or negative labels
(can turn off with rise in temperature). This also means that
multiple labels can mixed so that some turn on and some off with
rise and temperature, and vice versa.
[0077] Magnetocaloric materials can be engineered and therefore
tuned to have transitions at different magnetic fields and
temperatures. This means that these materials can be used as labels
so that they are visible or invisible at different magnetic fields
of MRI machines.
[0078] Referring to FIG. 2, in some implementations, the
magnetically manipulatable structure 135 is a magnetically
manipulatable structure 235 embedded within a sample 215 that is to
be imaged within an imaging apparatus 200. The imaging apparatus
200 includes a magnetic apparatus 205 that defines a sample volume
210 that is large enough to accommodate the sample 215 to be
imaged. The magnetically manipulatable structure 235 includes and
one or more magnetically manipulatable materials 236. The magnetic
apparatus 205 includes a magnet 220 that is configured to create a
magnetic field having a magnitude B in the sample 215. Each
magnetically manipulatable material 236 is a material that exhibits
a transition between a first magnetic state and a second magnetic
state in response to a change in a property associated with the
sample while the magnetic field having the magnitude B is
maintained in the sample. Thus, each magnetically manipulatable
material 236 can be a magnetocaloric material.
[0079] The apparatus 200 includes an energy supply 225 connected to
the magnet 220. The magnet 220 can be formed from electrically
conductive wire coils through which current from the energy supply
225 is passed. The energy supply 225 can provide a direct current
(DC) to the wire coils, which means that the energy supply 225
provides a constant voltage or current to the wire coils of the
magnet 220. Thus, the energy supply 225 can, for example, include
an alternating current (AC) generator equipped with a device to
produce the direct current, a device that converts AC to DC, or
batteries to provide DC. In some implementations, the magnet 220
can be a superconducting magnet.
[0080] In some implementations, the magnetic field magnitude B is
greater than 0.5 Tesla. In other implementations, the magnetic
field magnitude B is in a range of 1-20 Tesla. The magnitude B of
the magnetic field is limited by the design of the magnet 220.
Thus, for example, if the magnet 220 is a superconducting magnet,
then the magnitude B can be as large as 20 Tesla. The large value
of the magnitude B allows for higher-quality imaging, and the
superconductivity enable the imaging apparatus to work more
efficiently.
[0081] In some implementations, the first magnetic state of the
magnetically manipulatable material 236 is an antiferromagnetic
state or a paramagnetic state, which means that the magnetically
manipulatable material 236 is so weakly magnetic that it is
considered to be non-magnetic. In an antiferromagnetic state,
adjacent moments that behave as tiny magnets spontaneously align
themselves into opposite, or antiparallel, arrangements throughout
the magnetically manipulatable material 236 so that the material
236 exhibits almost no gross external magnetism. In
antiferromagnetic materials, the magnetism from magnetic moments
oriented in one direction is canceled out by the set of magnetic
moments that are aligned in the reverse direction. In a
paramagnetic state, some of the atoms or ions in the magnetically
manipulatable material 236 have a net magnetic moment due to
unpaired electrons in partially filled orbitals; however, the
individual magnetic moments do not interact magnetically, and the
magnetization is zero when a field is removed. In the presence of a
field, there is now a partial alignment of the atomic magnetic
moments in the direction of the field, resulting in a net positive
magnetization and positive susceptibility.
[0082] In some implementations, the second magnetic state of the
magnetically manipulatable material 236 is a ferromagnetic state or
a ferrimagnetic state, which means that the material is considered
to be magnetic. In a ferromagnetic state, the spins in the material
236 exhibit parallel alignment of moments resulting in large net
magnetization even in the absence of a magnetic field. In a
ferrimagnetic state, the opposing moments of the spins in the
material 236 are unequal and a spontaneous magnetization remains in
the absence of a magnetic field.
[0083] If the sample 215 is a living physiological or biological
tissue, then the magnetically manipulatable material 236 exhibits
the transition while the temperature in the sample is at a
physiological temperature, for example, between 270 and 370 Kelvin
(K).
[0084] The property associated with the sample 215 that is altered
can be a temperature. The transition occurs in response to a change
in temperature that is less than a fraction of the temperature of
the sample 215. For example, the change in temperature can be a
factor of ten times smaller than the temperature of the sample 215.
Thus, if the temperature of the sample 215 is about 270-370 K, then
the temperature change can be about 10-40 K.
[0085] The property associated with the sample 215 that is altered
can be a magnetic field of the sample. In this case, the transition
occurs in response to a change in a magnitude of a magnetic field
(.DELTA.B), where the change in magnitude .DELTA.B that is
substantially smaller than the magnitude B of the magnetic field.
The change in magnitude is substantially smaller than the magnitude
B if it is a fraction of the magnitude B, an order of magnitude
smaller than the magnitude B, or at least an order of magnitude
smaller than the magnitude B.
[0086] The imaging apparatus 200 also includes a sample property
scanning system 245 configured to change the property of the sample
215 while the magnetic field having magnitude B is maintained in
the sample 215. The sample property scanning system 245 therefore
acts to cause the transition in the magnetically manipulatable
material 236.
[0087] In some implementations, the sample property scanning system
245 includes a temperature scanning system for changing, as the
property, a temperature of the sample 215. The temperature scanning
system includes an apparatus thermally connected to the sample 215.
The thermally connected apparatus includes an induction heater that
operates at either a medium frequency or a radio frequency range
and includes a controller, and a heat inductor. The heat inductor
can be a heating coil.
[0088] In other implementations, the sample property scanning
system 245 includes a magnetic scanning system for changing, as the
property, a magnetic field of the sample 215. The magnetic scanning
system includes a magnetic source that is configured to change the
magnetic field of the sample 215.
[0089] In some implementations, the magnetic apparatus 205 is a
magnetic resonance imaging (MRI) apparatus. In this case, imaging
apparatus 200 can include, in addition to the magnet 220 shown in
FIG. 2, one or more gradient magnets 250 configured to produce a
variable magnetic field that ranges in strength an amount that is
much less than (for example, one hundredth of) the magnitude B.
This variable magnetic field can permit different parts of the
sample 215 to be scanned. The imaging apparatus 200 can also
include an electromagnetic source 255 configured to produce a
varying electromagnetic field having a range of magnetic field
magnitude that is much less than (for example, one hundredth of)
the magnitude B. The varying electromagnetic field can be a
radiofrequency field and can be produced by a set of coils that
transmit the radiofrequency waves into specific regions of the
sample 215.
[0090] If the magnetically manipulatable material 236 is not
inherently found in the sample 215, then it can be added to the
sample 215. For example, the imaging apparatus 200 can include a
delivery (or injection) apparatus 260 configured to transport the
magnetically manipulatable material 236 from a source 261 of the
material into the sample 215. The magnetically manipulatable
material 236 can be in the form of a plurality of
spatially-separated particles. The particles are dispersed
throughout at least one region of interest within the sample. If
the sample 215 is a living organism, then the size of the particles
can be on the order of the size of cells within the sample 215. For
example, the size of the particles is on the order of micrometers,
for example, 1-10 micrometers (.mu.m). In some implementations,
each particle has a microscopic size (which means it is only
viewable with the use of a microscope).
[0091] The particles of the magnetically manipulatable material 236
can be prepared prior to delivery into the sample 215 to be in a
suitable state for operation or use in the sample 215.
[0092] If the sample 215 is a living organism, the sample 215 is
held at a physiological temperature to maintain the organism in a
living state.
[0093] The imaging apparatus 200 includes a detector 270 that
detects a signal produced as a result of the interaction between
the magnetic field and the sample 215. The imaging apparatus 200
can also include some sort of output device 275 such as a display.
Additionally, the imaging apparatus includes a control system 240
connected to the magnetic apparatus 205. The control system 240 is
also connected to the other components of the imaging apparatus 200
such as the property scanning system 245, the electromagnetic
source 255, the gradient magnets 250, the injection apparatus 260,
the detector 270, the display 275, and the energy supply 225. The
control system 240 is configured to: receive data output from the
detector 270, the output relating to the detected signal; analyze
the received data; and estimate the sample property based on the
analysis. The control system 240 is also configured to create an
image of the sample 215 at the display 275 based on the
analysis.
[0094] The detector 270 detects the signal produced as a result of
the interaction between the magnetic field and the sample 215 by
detecting a signal produced by tissue within the sample 215 that is
in proximity to the magnetically manipulatable material 236. The
signal produced by tissue within the sample 215 that is in
proximity to the magnetically manipulatable material 236 includes
electromagnetic radiation generated from protons within the sample
215 in proximity to the magnetically manipulatable material
236.
[0095] The magnetically manipulatable material 236 remains
magnetically unsaturated while the magnetic field having the
magnitude B exists in the sample 215. This means that the
magnetically manipulatable material 236 is capable of exhibiting a
transition between the first magnetic state and the second magnetic
state even while the magnetic field having the magnitude B exists
in the sample 215.
[0096] In some implementations, the magnetically manipulatable
structure 235 includes one or more different magnetically
manipulatable materials 236 or magnetocaloric materials. In these
implementations, each different magnetically manipulatable material
236 in the structure can have a transition that occurs in response
to a distinct change in the property of the sample 215. For
example, a first magnetically manipulatable material 236 has a
transition from the first magnetic state to the second magnetic
state that occurs in response to an increase in the sample
property; and a second magnetically manipulatable material 236 has
a transition from the first magnetic state to the second magnetic
state that occurs in response to a decrease in the sample property.
As another example, a first magnetically manipulatable material 236
has a transition from the first magnetic state to the second
magnetic state that occurs in response to an increase in the sample
property; and a second magnetically manipulatable material 236 has
a transition from the second magnetic state to the first magnetic
state that occurs in response to an increase in the sample
property. As a still further example, a first magnetically
manipulatable material 236 has a transition between the first
magnetic state and the second magnetic state that occurs in
response to a change in a first sample property; and a second
magnetically manipulatable material 236 has a transition between
the first magnetic state and the second magnetic state that occurs
in response to a change in a second sample property that is
distinct from the first sample property.
[0097] In other implementations, the transition from the first
magnetic state to the second magnetic state occurs in a first range
of values of the property as the property is increased; the
transition from the second magnetic state to the first magnetic
state occurs in a second range of values of the property as the
property is decreased; and the first range of values is distinct
from the second range of values.
[0098] FIG. 3A shows a magnetic state M (or magnetic moment) of the
magnetically manipulatable material 236 versus the sample property,
where the sample property is the temperature T of the sample 215.
In the implementation shown in FIG. 3A, the magnetically
manipulatable material 236 transitions from a first magnetic state
300 to a second magnetic state 305 at a transition temperature
T(tr). In this implementation, the first magnetic state 300 is
magnetic, for example, ferromagnetic or ferrimagnetic, and the
second magnetic state 305 is non-magnetic, for example, an
antiferromagnetic or a paramagnetic. Moreover, this transition
occurs while the magnetic field having the magnitude B is
maintained in the sample 215, where the magnitude B is a value
between 1-10 T. The transition temperature T(tr) can be between 270
K and 370 K or around 310 K.
[0099] FIG. 3B shows a magnetic state M (or magnetic moment) of the
magnetically manipulatable material 236 versus the sample property,
where the sample property is the temperature T of the sample 215.
In the implementation shown in FIG. 3B, the magnetically
manipulatable material 236 transitions from a first magnetic state
310 to a second magnetic state 315 at a transition temperature
T(tr). In this implementation, the first magnetic state 310 is
non-magnetic, for example, antiferromagnetic or paramagnetic, and
the second magnetic state 315 is magnetic, for example,
ferromagnetic or ferrimagnetic. Moreover, this transition occurs
while the magnetic field having the magnitude B is maintained in
the sample 215, where the magnitude B is a value between 1-10 T.
The transition temperature T(tr) can be between 270 K and 370 K or
around 310 K.
[0100] FIG. 4 shows a magnetic state M (or magnetic moment) of the
magnetically manipulatable material 236 versus the sample property,
where the sample property is the magnetic field (represented by the
magnitude B) within the sample 215. In the implementation shown in
FIG. 4, the magnetically manipulatable material 236 transitions
from a first magnetic state 400 to a second magnetic state 405 at a
first transition magnetic field magnitude B1(tr), and from the
second magnetic state 405 to a third magnetic state 410 at a second
transition magnetic field magnitude B2 (tr). In this
implementation, the first magnetic state 400 is non-magnetic, for
example, antiferromagnetic or paramagnetic; the second magnetic
state 405 is also non-magnetic, and the third magnetic state 410 is
magnetic. Moreover, these transitions occur while the temperature
within the sample 215 is maintained at a temperature T, which can
have a value between 270 K and 370K or around 310K. The magnitude
B1(tr) can be any value between 1-10 T, for example 4 T, and the
magnitude B2(tr) can be any other value between 1-10 T, for
example, 5 T.
[0101] FIG. 5A shows a magnetic state M (or magnetic moment) of the
magnetically manipulatable material 236 versus the sample property,
where the sample property is the magnetic field (represented by the
magnitude B) within the sample 215, while maintaining the sample
215 at a constant temperature T. The transition from the first
magnetic state 500 to the second magnetic state 505 occurs at a
magnitude B1(tr) while the magnitude B is increased. On the other
hand, the transition from the second magnetic state 505 to the
first magnetic state 500 occurs at a different magnitude B2(tr)
while the magnitude is decreased. The magnitude B2(tr) is less than
the magnitude B1(tr). This is because of the hysteresis effect (in
which the physical effect, that is, the magnetic state M, on the
sample 215 is retarded or changed depending how the sample property
is changed).
[0102] FIG. 5B shows a magnetic state M (or magnetic moment) of the
magnetically manipulatable material 236 versus the sample property,
where the sample property is the temperature (represented by T)
within the sample 215, while maintaining the sample 215 at a
constant magnetic field magnitude B. The transition from the first
magnetic state 510 to the second magnetic state 515 occurs at a
temperature T1(tr) while the temperature T is increased. On the
other hand, the transition from the second magnetic state 515 to
the first magnetic state 510 occurs at a different temperature
T2(tr) (which is less than the temperature T1(tr)) while the
temperature T is decreased because of the hysteresis effect.
[0103] Furthermore, it is possible that the magnetically
manipulatable material 236 only exhibits a transition in response
to a change in two sample properties.
[0104] As mentioned above, and referring to FIG. 6A, the
magnetically manipulatable structure 235 can include a plurality of
different magnetically manipulatable materials 236 (that is, two or
more magnetically manipulatable materials) within the sample 215.
In this example, there are two magnetically manipulatable materials
236a and 236b contained or embedded within the sample 215. FIG. 6B
shows an example of a graph of a magnetic state M (or magnetic
moment) of the two magnetically manipulatable materials 236a, 236b
within the sample 215 versus the sample property, where the sample
property is the magnetic field (represented by the magnitude B)
within the sample, while maintaining the sample 215 at a constant
temperature T. In this implementation, the two magnetically
manipulatable materials 236a, 236b have different transition points
in response to a change in the magnetic field magnitude B.
[0105] The behavior of the first magnetically manipulatable
material 236a is shown in the red graph 602 and the behavior of the
second magnetically manipulatable material 236b is shown in the
green graph 612. The first magnetically manipulatable material 236a
transitions from its first magnetic state 600 to its second
magnetic state 605 at a magnetic field magnitude B1(tr) as the
magnetic field magnitude B is being increased while the first
magnetically manipulatable material 236a transitions from its
second magnetic state 605 to its first magnetic state 600 at a
magnetic field magnitude B2(tr) as the magnetic field magnitude B
is being decreased. The second magnetically manipulatable material
236b transitions from its first magnetic state 610 to its second
magnetic state 615 at a magnetic field magnitude B3(tr) as the
magnetic field magnitude B is being increased while the second
magnetically manipulatable material 236b transitions from its
second magnetic state 615 to its first magnetic state 610 at a
magnetic field magnitude B4(tr) as the magnetic field magnitude B
is being decreased. These transitions points B1(tr), B2(tr),
B3(tr), and B4(tr) are distinct from each other. For example, if
the magnetic field magnitude B generally remains between 1-10 T and
the temperature at which the sample 215 is held is about 310 K,
then the transition point B1(tr) can be 4.4 T, the transition point
B2(tr) can be 3.7 T, the transition point B3(tr) can be 6.7 T, and
the transition point B4(tr) can be 5.7 T. In this example, both of
the magnetically manipulatable materials 236a, 236b are
non-magnetic below 3.7 T, both of the magnetically manipulatable
materials 236a, 236b are magnetic above 6.7 T, and the first
magnetically manipulatable material 236a is magnetic while the
second manipulatable material 236b is non-magnetic at 4.7 T.
[0106] In some implementations, the magnetically manipulatable
material 236 transitions from a magnetic to a non-magnetic state
with a rise in the sample property. For example, as shown in FIG.
7A, a first magnetically manipulatable material transitions from a
magnetic state 700 to a non-magnetic state 705 at the transition
temperature T1(tr) as the sample property of temperature T is
increased while the first magnetically manipulatable material
transitions from the non-magnetic state 705 to the magnetic state
700 at the transition temperature T2(tr) as the sample property of
temperature T is decreased. In this example, the magnetic field
magnitude B is held constant. As an example, the material
Iron--Lanthanum--Silicon (Fe--La--Si) behaves in this manner.
[0107] In other implementations, the magnetically manipulatable
material 236 transitions from a non-magnetic to a magnetic state
with a rise in the sample property. For example, as shown in FIG.
7B, a second magnetically manipulatable material transitions from a
non-magnetic state 710 to a magnetic state 715 at the transition
temperature T3(tr) as the sample property of temperature T is
increased while the second magnetically manipulatable material
transitions from the magnetic state 715 to the non-magnetic state
710 at the transition temperature T4(tr) as the sample property of
temperature T is decreased. In this example, the magnetic field
magnitude B is held constant. For example, the material FeRh
behaves in this manner.
[0108] If both the first and the second magnetically manipulatable
materials of FIGS. 7A and 7B are within the sample 215, such as
shown in FIG. 6A, then an exemplary combined transition graph is
shown in FIG. 8 in which the transition temperature T3(tr) is equal
to the transition temperature T1(tr) and the transition temperature
T4(tr) is equal to the transition temperature T2(tr). In this
implementation, the first and second magnetically manipulatable
materials 236a, 236b can be switched on an off (that is,
transitioned from the magnetic state to the non-magnetic state) in
opposite manners. For example, the second magnetically
manipulatable material 236b is magnetic and the first magnetically
manipulatable material 236a is non-magnetic above the transition
temperature T3(tr) (and T1(tr)) while the first magnetically
manipulatable material 236a is magnetic and the second magnetically
manipulatable material 236b is non-magnetic below the transition
temperature T4(tr) (and T4(tr)). In this example, the temperature
can be adjusted in a range of 250 K to 350 K.
[0109] While only two magnetically manipulatable materials 236a and
236b are discussed above, it is possible for the magnetically
manipulatable structure 235 to include more than two different
types of these materials.
[0110] Referring to FIG. 9, in other implementations, the
magnetically manipulatable structure 135 is a magnetically
manipulatable structure 935 embedded within a sample 915 of an
apparatus 900. The apparatus 900 is designed to use magnetocaloric
materials as physical actuators of biological constructs in
genetically-modified cells while in a DC magnetic field. For
simplicity, components shown in FIG. 9 are merely in block diagram
form and are not to scale. A change to a property of the
magnetocaloric material causes a change in the status of the
biological construct because the magnetocaloric material is
physically coupled with the biological construct. A physical
coupling means that there is a coupling that is based on an
exchange of matter or energy. For example, the physical coupling
could be a thermal coupling. As another example, the physical
coupling could be an electromagnetic coupling. The property of the
magnetocaloric material that can be changed can be its magnetic
state. The property of the magnetocaloric material that can be
changed can be its temperature.
[0111] In some implementations, and as described herein, the
property of the magnetocaloric material that is changed is the
temperature, and the temperature of the magnetocaloric material is
changed by a change in magnitude B of the magnetic field applied to
the sample 915. In these implementations, the physical coupling
between the magnetocaloric material and the biological construct is
a thermal coupling and the biological construct is a
thermally-sensitive biological construct.
[0112] The apparatus 900 includes a magnetic apparatus 905 that
defines an actuation volume 910 that is large enough to accommodate
the sample 915. The magnetic apparatus 905 includes a magnet 920
that is configured to create a magnetic field having a magnitude B
in the sample 915 when supplied with a DC current from a DC energy
supply 925.
[0113] The apparatus 900 includes at least one thermally-sensitive
biological construct 930 within the sample 915. The magnetically
manipulatable structure 935 is a magnetocaloric actuator 935
thermally coupled with the thermally-sensitive biological construct
930. While one construct 930 and one actuator 935 is shown, it is
possible to have a plurality of constructs 930 or a plurality of
actuators 935 associated with each construct. Thermal coupling
between two elements means that the heat is freely conducted
between those two elements. Thus, heat is able to be thermally
conducted between the biological construct 930 and the actuator
935. Thermal coupling between two elements can mean that the two
elements are near enough to each other so that heat does not
dissipate substantially into the sample 915 before being conducted
between the two elements. Thermal coupling between two elements can
mean that the two elements have relative sizes that are
complementary so that heat transfer between the two elements is
enabled.
[0114] A change in the magnitude B of the magnetic field supplied
with the DC current from the supply 925 to the magnet 920 causes
the temperature of the magnetocaloric actuator 935 to change, and
this change causes a change in a status of the thermally-sensitive
biological construct 930.
[0115] The apparatus 900 therefore operates under the application
of a DC magnetic field, or a magnetic field that is very close to
DC. That is, the magnetic field changes relatively slowly at the
location of the actuator 935.
[0116] The apparatus 900 also includes a control system 940
connected to the DC energy supply 925 to control the operation of
the DC energy supply 925.
[0117] The magnetocaloric actuator 935 can include one or more
magnetically manipulatable materials 936i. The magnetically
manipulatable material 936i exhibits a transition between a first
magnetic state and a second magnetic state in response to the
change in the magnitude B of the magnetic field produced by the
magnet 920. For example, the magnetically manipulatable material
936i of the actuator 935 exhibits the transition while the
temperature in the sample 915 is between 270 and 370 K. The
magnetically manipulatable material 936i of the actuator 935 can
include a material selected from the group consisting of
iron-rhodium (FeRh), alloys of iron-rhodium, alloys of manganese
arsenide, Heusler alloys, alloys of manganese-iron, alloys of
lanthanum, iron, and silicon, and gadolinium.
[0118] Each magnetically manipulatable material 936i is a
spatially-separated particle having a size that is large enough to
retain heat long enough to cause the change in status in the
thermally-sensitive biological construct 930. For example, a cell
in a living organism can be between 1-50 .mu.m in diameter. If the
biological construct 930 is on the order of a nanometer (nm), then
the magnetocaloric actuator 935 can have a size on the order of
about 1-100 .mu.m.
[0119] The sample 915 can be a region of a live human body. In this
implementation, the magnetically manipulatable material 936i of the
actuator 935 exhibits the transition while the temperature in the
live human body region is at a human body temperature. In some
implementations, the sample 915 is a living organism and the sample
915 is held at a physiological temperature to maintain the organism
in a living state.
[0120] The transition between the first magnetic state and the
second magnetic state of the magnetically manipulatable material
936i can occur in response to a change in a magnitude of a magnetic
field that is substantially smaller than the overall magnitude B of
the magnetic field produced by the magnet 920.
[0121] The temperature change caused to the magnetocaloric actuator
935 occurs without causing a change in status of materials within
the sample 915 other than the at least one thermally-sensitive
biological construct 930. In this way, the apparatus 900 is able to
finely heat and cool in local areas of the sample 915 without
causing large-scale heating or cooling to other areas of the sample
915.
[0122] In some implementations, the magnet 920 includes
electrically conductive wire coils through which current from the
DC energy supply 925 is passed. Thus, the DC energy supply 925
provides the DC current supplied to the wire coils. In some
implementations, the magnet 920 is a superconducting magnet. And,
the magnetic apparatus 905 can be a magnetic resonance imaging
apparatus.
[0123] Moreover, the magnetic field magnitude B is greater than 0.5
Tesla or in a range of 1-20 Tesla. The magnitude B of the magnetic
field can be in a range that does not cause any detrimental changes
to the sample 915. That is, the sample 915 does not deteriorate or
degrade due to the magnitude B of the magnetic field that is
created.
[0124] The temperature change dT that occurs in the magnetocaloric
actuator 935 is governed by the following equation.
dT = - T C B .times. ( .differential. M .differential. T ) B dB ,
##EQU00001##
where T is the temperature of the magnetocaloric actuator 935,
C.sub.B is the heat capacity of the magnetocaloric actuator 935,
.differential.M/.differential.T is the slope of the magnetization M
of the magnetocaloric actuator 935 versus the temperature T at the
specific magnetic field B, and dB is the change in magnetic field
applied to the magnetocaloric actuator 935 by the magnet 920. The
temperature T of the actuator 935 changes as the magnetic field
magnitude B changes. Moreover, the slope
.differential.M/.differential.T is an inherent property of the
magnetocaloric actuator 935. As an example, the magnetocaloric
actuator temperature change dT is at least 5.degree. C. for a
change in magnitude of the magnetic field dB between 1-20 T.
[0125] In another example, if the magnetic field B supplied by the
magnet 920 changes from 0 T to 2 T, then the value of dB is 2 T. As
another example, if the magnetic field B supplied by the magnet 920
changes from 3 T to 5 T, then the value of dB is 2 T. The
magnetically manipulatable materials 936i that are selected for the
magneto-caloric actuator 935 are selected to provide a temperature
change dT for as small a change in magnetic field B. Thus, the
value of .differential.M/.differential.T for the magnetically
manipulatable materials 936i is as large as possible or at a
maximum at typical physiological (biological) temperatures T (for
example, around 37.degree. C.). In particular, materials 936i that
have suitable values of .differential.M/.differential.T include
gadolinium and FeRh. Other materials can have a large value of
.differential.M/.differential.T at temperatures T that are not
typical physiological or biological temperatures, and those other
materials would not be suitable for use in a physiological or
biological sample 915.
[0126] If the magnetic apparatus 205 is an MRI machine, then the
apparatus 900 can include one or more of the other components for
operating the MRI machine. For example, the apparatus 900 can also
include one or more of the property scanning system 245 (which is
used to scan or change the magnetic field of the sample 915 in this
implementation), the electromagnetic source 255, the gradient
magnets 250, the detector 270, and the display 275.
[0127] FIGS. 10A and 10B are block diagrams of an implementation in
which the at least one thermally-sensitive biological construct 930
within the sample 915 is an ion channel 1030 positioned along a
cellular structure 1017 (for example, a cell membrane) of the
sample 915. The at least one magnetocaloric actuator 1035 is a
magnetocaloric actuator 1035 that includes a plurality of
magnetically manipulatable materials 936i near the ion channel
1030. The ion channel 1030 has a status that is either closed (FIG.
10A) or open (FIG. 10B). For example, when closed, the ion channel
1030 blocks other elements (such as molecules, ions, or atoms)
nearby and within the sample 915 from passing through the cellular
structure 1017. When open, the ion channel 1030 permits these other
nearby elements (such as molecules, ions, or atoms) to freely pass
through the cellular structure 1017 as long as the opening is large
enough to accommodate the size of the element.
[0128] Temperature sensitive ion channels 1030 can be integrated
into the cell membrane (the cellular structure 1017) using a
suitable technique such as cloning or genetic engineering. For
example, the ion channel 1030 can be genetically engineered into
the cellular structure 1017. This means that the ion channel 1030
may not be present in the wild-type or non-engineered cellular
structure 1017 of the sample 915. The cellular structure 1017 can
be genetically altered through the exogenous delivery of a portion
of deoxyribonucleic acid (DNA) comprising a gene that expresses the
ion channel 1030 in the sample 915. For example, transgenic
expression of a temperature-activated ion channel in a cell
comprising the sample 915 leads to the insertion of the ion channel
1030 into the cell membrane, identified as the cellular structure
1017.
[0129] In some implementations, the ion channel 1030 is a transient
receptor potential cation channel subfamily V member (such as TRPV1
or TRPV4). The TRPV channel changes its state from closed to open
by warming up by about 5-10.degree. C. Thus, the change in
magnitude B of the magnetic field supplied to the sample 915 should
be large enough to increase the temperature of the magnetocaloric
actuator 1035 by enough of an amount such that the temperature of
the TRPV increases by about 5.degree. C.
[0130] As another example, the ion channel 1030 is a transient
receptor potential cation channel subfamily M member (such as
TRPM8). By contrast, the TRPM channel changes its state from closed
to open by cooling down by about 5-10.degree. C. Thus, the change
in magnitude B of the magnetic field supplied to the sample 915
should be large enough to decrease the temperature of the
magnetocaloric actuator 1035 by enough of an amount so that the
temperature of the TRPM decreases by about 5.degree. C.
[0131] Referring also to FIG. 9, in some implementations, an
increase in the magnitude B of the magnetic field supplied with the
DC energy supply 925 causes an increase in the temperature of the
magnetocaloric actuator 935 and an increase in the temperature of
the thermally-sensitive biological construct 930. And, a decrease
in the magnitude B of the magnetic field supplied with the DC
energy supply 925 causes a decrease in the temperature of the
magnetocaloric actuator 935 and a decrease in the temperature of
the thermally-sensitive biological construct 930. For example, a
magnetocaloric actuator 1035 in which its magnetically
manipulatable material 936i includes gadolinium exhibits this
property. For example, the temperature of gadolinium (as the
magnetically manipulatable material 936i) increases by about
2.5-3.0.degree. C. for every 1 T increase in the magnitude B of the
magnetic field at a physiological or biological temperature.
[0132] In other implementations, an increase in the magnitude B of
the magnetic field supplied with the DC energy supply 925 causes a
decrease in the temperature of the magnetocaloric actuator 935 and
a decrease in the temperature of the thermally-sensitive biological
construct 930. Moreover, a decrease in the magnitude B of the
magnetic field supplied with the DC energy supply 925 causes an
increase in the temperature of the magnetocaloric actuator 935 and
an increase in the temperature of the thermally-sensitive
biological construct 930. A magnetocaloric actuator 935 in which
its magnetically manipulatable material 936i includes an alloy of
iron-rhodium (FeRh) exhibits this property. For example, the
temperature of FeRh (as the magnetically manipulatable material
936i) decreases by about 6.5.degree. C. for every 1 T increase in
the magnitude B of the magnetic field at a physiological or
biological temperature.
[0133] Thus, in this way, the apparatus 900 can be used to either
heat or cool the actuator 935, and because of this flexibility,
there are more options for how to affect the thermally-sensitive
biological construct 930.
[0134] FIG. 11 is a block diagram of a sample 1115 that includes a
plurality of thermally-sensitive biological constructs 1130A,
1130B, . . . 1130K (where K is an integer greater than 2). In some
implementations, these biological constructs 1130A, 1130B, . . .
1130K can be associated with the same structure within the sample
1115. In other implementations, one or more of these biological
constructs 1130A, 1130B, . . . 1130K are associated with a
structure that is different from the structures associated with the
other biological constructs. Moreover, a magnetocaloric actuator
1135 can be associated with each of these biological constructs.
For example, a magnetocaloric actuator 1135i is thermally coupled
with a first thermally-sensitive biological construct 1130A, a
magnetocaloric actuator 1135j is thermally coupled with a second
thermally-sensitive biological construct 1130B, . . . and a
magnetocaloric actuator 1135k is thermally coupled with a last
thermally-sensitive biological constructs 1130K. Each
magnetocaloric actuator 1135i, 1135j, . . . 1135k is distinct from
each of the other magnetocaloric actuators.
[0135] FIG. 12 is a block diagram of a single magnetocaloric
actuator 1235 having different magnetically manipulatable materials
1236i, 1236j, 1236k that are mixed together (but do not interact
with each other). The labels i, j, and k denote three different
types of materials. While only three are shown there can be any
number of different materials in the magnetocaloric actuator 1235.
For example, the material 1236i can heat up as the magnetic field
is decreased while the material 1236j can cool down as the magnetic
field is decreased.
[0136] Referring again to FIG. 9, the apparatus 900 works with a
change in magnetic field that is caused by a DC current from the DC
energy supply 925, and thus a thermal magnetic treatment in a
biological or medical sample 915 is enabled without the use of AC
or RF (radio frequency) fields, which can cause more damage to the
sample 915. In Tesla-scale magnetic fields (such as those used in
modern magnetic resonance imaging or NMR spectrometers),
temperature differences obtained by the magnetocaloric actuator 935
can be on the order of 10.degree. C. or more. Furthermore, in the
implementations of FIGS. 10A and 10B, in which the
thermally-sensitive biological construct 1030 is an ion channel
1030 positioned along a cellular structure 1017 of the sample 915,
these ion channels 1030 can be inserted into biological cells such
as neurons, that are sensitive to heat and cold. Temperature
differences on the order of 5-10.degree. C. are large enough to
open or close such ion channels 1030. Therefore, magnetically
manipulatable materials 936i can be on the order of a micron in
size (for example 10 .mu.m in diameter), and placed next to such
cells, which can be activated by exposing them to magnetic fields
that change due to changes supplied by a DC energy supply 925. In
this way, the ion channel 1030 can be remotely activated, which
means that an invasive procedure that disrupts the sample 915 is
not needed in order to activate the ion channel 1030.
[0137] Referring to FIG. 13, a test apparatus 1300 is shown for
demonstrating the feasibility of using magnetocaloric materials as
thermal actuators of temperature-sensitive biological constructs in
genetically-modified cells while in a DC magnetic field. FIG. 13
shows a schematic representation of the test apparatus 1300 in
which the at least one thermally-sensitive biological construct 930
within the sample 915 is an ion channel (such as discussed above)
1330 positioned in a cellular structure 1317 of a neuron 1318
within a biological sample 1315. The behavior of the neurons 1318
in the sample 1315 is tested with conductors 1319, through which
current flows to a current measurement device 1336, and the current
value is an indicator of whether the neurons fire in response to
some stimulus.
[0138] In this test, some of the neurons 1318B are configured with
ion channels 1330 while some of the neurons 1318A lack any ion
channels 1330. Moreover, some of the neurons 1318A that lack ion
channels are thermally coupled with at least one magnetocaloric
actuator 1335 while the others of the neurons 1318A that lack ion
channels are not thermally coupled with a magnetocaloric actuator
1335. Similarly, some of the neurons 1318B with the ion channels
1330 are thermally coupled with at least one magnetocaloric
actuator 1335 while the others of the neurons 1318B with the ion
channels 1330 are not thermally coupled with a magnetocaloric
actuator 1335. The test apparatus 1300 includes at least one
conductor 1319 associated with each neuron 1318. Thus, the
conductor 1319 registers a change in current when the neuron 1318
fires. Moreover, the test apparatus 1300 can be configured so that
a neuron 1318B only fires when it is activated by the opening or
closing of its ion channel 1330. In this way, the effect of the ion
channel 1330 changing its state (between open and close) can be
measured or detected with the current signal measured from the
conductor 1319.
[0139] To test, the sample 1315 is placed in an actuation volume
(such as volume 910) and a magnetic field having a magnitude B is
applied by the magnet (such as magnet 920). The magnitude B of the
magnetic field is changed (for example, by changing the DC current
from the DC energy supply 925). The change of the magnitude B of
the magnetic field causes the temperature of the magnetocaloric
actuator 1335 to change, and this temperature change causes a
change in status of the ion channel 1330 that is thermally coupled
to a magnetocaloric actuator 1335, and this change in status of the
ion channel 1330 causes the neuron 1318B to which it is associated
or in proximity of to fire (or change its current output). Thus, it
is expected that the change in magnitude B of the magnetic field
leads to only a change in current output of the neurons 1318B that
are associated with ion channels 1330 that are in thermal coupling
with an actuator 1335, while the neurons 1318B having ion channels
1330 that are not in thermal coupling with an actuator 1335 and the
neurons 1318A should not produce any change in current output.
[0140] Switchable and tunable labels with high contrast ratio are
developed for MM using magnetocaloric materials that have sharp
first order magnetic phase transitions at physiological
temperatures and typical MRI magnetic fields. Selection of
appropriate magnetic materials for tunable labels in typical MRI
settings of Tesla-scale DC magnetic fields and physiological
temperatures of around 37.degree. C. is hampered by the basic
physical properties of most classical magnetic materials such as
iron, iron oxides, and the like. Most magnetic materials have Curie
temperatures in the hundreds of degrees Celsius, and therefore have
a very flat saturation magnetization with respect to temperature at
the physiological body temperatures of around 37.degree. C. (310K).
Moreover, standard MRI settings place these labels in large DC
magnetic fields typically between 1-20 Tesla where all of these
materials are magnetically saturated and therefore have constant
contrast in the MRI. Therefore, magnetic materials are identified,
designed, or engineered that have switchable and tunable properties
with high differential contrast ratios in the MRI settings where
the DC magnetic fields are very large (on the scale of Teslas) and
in-vivo physiological temperatures are around 37.degree. C.
[0141] A magnetocaloric material such as iron-rhodium (FeRh) can be
prepared by melt mixing, high-temperature annealing, and ice-water
quenching. Temperature and magnetic field dependent magnetization
measurements of wire-cut FeRh samples can be performed on a
vibrating sample magnetometer. Temperature-dependent MRI of FeRh
samples can be performed on 4.7T scanner.
[0142] The magnetocaloric material FeRh can be demonstrated to act
as a high contrast ratio switchable MM contrast agent due to its
sharp first order magnetic phase transition in DC magnetic field of
MRI and at the physiologically relevant temperature. A wide range
of magnetocaloric materials are available that can be tuned by
materials science techniques to optimize their response under
MRI-appropriate conditions and be controllably switched in-situ
with temperature, magnetic field, or a combination of both.
[0143] Examples of the apparatus, materials, and tests performed on
these magnetically manipulatable materials 236 or 936i using the
apparatus are described next.
[0144] Moreover, the development of novel contrast mechanisms and
labeling agents for MRI facilitates further the advancements in
non-invasive cell imaging, tracking, and readout of physiological
conditions in-vivo. More specifically, the extremely sharp
first-order magnetic phase transitions these magnetocaloric
materials have at typical physiological temperatures and in the
presence of the large DC magnetic field values associated with MM
machines provide an ideal match to the requirements for the design
of novel MRI labels. Furthermore, a wide range of magnetocaloric
materials are available that can be engineered and fine-tuned to
optimize their response under MRI-appropriate conditions.
[0145] One magnetocaloric material that can be used is
iron-rhodium, which is discussed next. The iron-rhodium is prepared
by mixing the components (Fe and Rh) in an arc melting furnace.
Next, the mixed components are subjected to a high-temperature
annealing in an Argon gas quartz tube furnace at 1,000.degree. C.
for two weeks, and subsequently rapidly quenched in ice-water. This
procedure typically results in the ordered (body-centered-cubic
CsCl-type crystal structure) binary alloy FeRh with the bulk
saturation magnetization of Ms=1.3.times.10.sup.6 A/m in the
ferromagnetic state. The prepared FeRh can be cut into mm-scale
sample disks and buffed to a shiny metallic surface with an optical
fiber polishing paper in order to remove any oxide from the
samples. Temperature and field dependent magnetic measurements of
the samples can be performed in a 9-Tesla Vibrating Sample
Magnetometer (for example, procured from VSM, Quantum Design,
Inc.). In order to demonstrate the basic proof-of-concept
feasibility of a magnetocaloric material as a tunable and
switchable high differential contrast agent at physiological
temperatures and typical MM settings, a 4.7 Tesla MM scanner
(produced by Bruker Biospin, Inc.) can be used. The available MRI
polarizing magnetic field of such a scanner is closest to the value
where the sharp first order magnetic phase transition happens near
the physiological temperature of 37.degree. C. (310.degree. K).
[0146] Two sets of iron-rhodium granules are prepared for testing.
The first set is Fe 49%-Rh 51% atomic composition, of 99% nominal
purity and is discussed with reference to FIGS. 14A and 15A and the
second set is Fe 49%-Rh 51% atomic composition, of 99.9% nominal
purity) and is discussed with reference to FIGS. 14B and 15B. The
granules of FeRh can be obtained from American Elements Corporation
(Model FE-RH-02 for 99% purity or Model FE-RH-03 for 99.9%
purity).
[0147] In FIGS. 14A-15B, the magnetocaloric material (236 or 936i)
used in the magnetically manipulatable structure is FeRh. FIGS. 14A
and 14B show the measurements of the magnetic moment of the FeRh
structure as a function of temperature at different constant
magnetic fields. Measurements are taken with the 9T vibrating
sample magnetometer. Both FeRh structures exhibited a sharp first
order magnetic transition from an antiferromagnetic to a
ferromagnetic state over a very narrow range of physiologically
relevant temperatures, as discussed next.
[0148] FIG. 14A shows the measurement of the magnetic moment of a
99% purity FeRh structure as a function of temperature in different
bias DC magnetic fields, for example, 1T (1401A), 3T (1403A), and
5T (1405A). The FeRh structure exhibits a sharp magnetic phase
transition from an antiferromagnetic to a ferromagnetic state over
a very narrow range of physiologically relevant temperatures. More
specifically, the FeRh structure has a sharp transition around body
temperature (37.degree. C.=310K) in a constant magnetic field (the
DC bias field) of around 1 Tesla.
[0149] FIG. 14B shows the measurement of the magnetic moment of a
99.9% purity FeRh structure as a function of temperature in
different bias DC magnetic fields, for example, 1T (1401B), 3T
(1403B), 5T (1405B), and 7T (1407B). The FeRh structure exhibits a
sharp transition from an antiferromagnetic to a ferromagnetic state
over a very narrow range of physiologically relevant temperatures.
More specifically, the FeRh structure has a sharp magnetic phase
transition around body temperature (37.degree. C.=310K) in the DC
bias field of around 5 Tesla.
[0150] These results are in line with the previously reported
measurements of FeRh and demonstrate several features. The most
important one is that the magnetization of FeRh changes through the
transition by a factor of about 20 in absolute value, and it does
so over a very narrow temperature range around the physiological
body temperature and in the presence of a large Tesla-scale
magnetic field. The second feature is that the temperature
dependence and magnetic properties of FeRh (and magneto-caloric
materials in general) are highly dependent on the purity of the
FeRh. Conversely, this demonstrates the attractive feature of FeRh
(and other magneto-caloric materials) that, through careful
materials science preparation and process control of impurities and
crystal structure, one can tune and engineer FeRh to have a sharp
magnetic phase transition at the desired temperature and bias
magnetic field (nominally at the physiological body temperature and
magnetic field of the MRI machine used). Furthermore, such
temperature dependence of magnetization demonstrates that, once the
proper magneto-caloric material is prepared for a specific magnetic
field of the MRI used, the magnetization of that magneto-caloric
label can in principle be switched in-situ by modest temperature
changes on the order of a few degrees Celsius.
[0151] FIGS. 15A and 15B show the measurements of the magnetic
moment of the FeRh structure as a function of varying magnetic
field at constant temperature (at a room temperature of 27.degree.
C.=300K or at a physiological body temperature of 37.degree.
C.=310K, respectively). Measurements are taken with the 9T
vibrating sample magnetometer.
[0152] Referring to FIG. 15A, the magnetization of the FeRh
structure is tuned with the magnetic field. In this measurement,
the magnetic moment of a 99% purity FeRh structure is measured as a
function of the magnetic field at various constant temperatures,
for example, 310K (1510A) and 300K (1500A). As evident, the sharp
transition is present at large DC magnetic field values and around
physiologically relevant temperatures.
[0153] Referring to FIG. 15B, the magnetization of the FeRh
structure is tuned with the magnetic field. In this measurement,
the magnetic moment of a 99.9% purity FeRh structure is measured as
a function of the magnetic field at various constant temperatures,
for example, 330K (1530B), 320K (1520B), 310K (1510B), and 300K
(1500B). Again, the sharp transition is present at large DC
magnetic field values and around physiologically relevant
temperatures.
[0154] Specifically, the 99% purity FeRh structure (FIG. 14A) has a
sharp magnetic phase transition around the room and body
temperatures at the magnetic field values between 0.5-2 Tesla,
while the 99.9% purity FeRh structure (FIG. 14B) has a sharp
magnetic phase transition around the room and body temperatures at
the magnetic field values between 4-6 Tesla. These results
demonstrate another feature that, once the proper magnetocaloric
material is fabricated as a switchable MRI label for the specific
magnetic field of the MM used, the magnetization of that
magnetocaloric label can be switched in-situ with additionally
added or subtracted magnetic field or by temporarily removing the
sample from the MM bore.
[0155] Measurements described in FIGS. 14A, 14B, 15A, and 15B guide
experimental choices for demonstrating the basic proof-of-concept
feasibility of a magnetocaloric FeRh material as a switchable high
differential contrast MM agent. Of the two FeRh structures that
were prepared, 99.9% purity FeRh structure displayed a sharper
first order magnetic transition at a higher bias DC magnetic field
(of around 5 Tesla) at the physiological temperature of 37.degree.
C. Referring to FIG. 16, for the MRI demonstration, a testing
apparatus 1690 is used. In the testing apparatus 1690, the disk of
FeRh 1635 is embedded in agarose 1680 next to an MM-compatible
optical fiber-based thermometer 1681 (which can be procured from
FISO Technologies, Inc.). The disk 1635 and the agarose 1680 are
held within a container 1682, which is sealed with a cap 1683. The
container 1682 is wrapped in tubing 1684 connected to a
temperature-controlled water circulating bath in order to sweep and
control the temperature of the disk 1635 and its environment around
physiologically relevant temperature range (10-55.degree. C.).
[0156] The testing apparatus 1690 of FIG. 16 can be used to create
representative gradient-echo images of the effect of the mm-scale
disk of FeRh 1635 on the surrounding agarose 1680 as the
temperature is swept from the antiferromagnetic phase below the
transition temperature to the ferromagnetic phase above the
transition temperature of the FeRh structure 1635 and then cooled.
In order to produce a gradient-echo image, the testing apparatus
1690 is inserted into a magnet (such as the magnet 120, which in
this test case is an MRI magnet). RF pulses and gradient pulses are
applied to the entire FeRh structure 1635. The resonant signal from
the surrounding agarose 1680 is detected by inductive detection
coils of the magnetic apparatus 105 (which is an MRI machine) in
which the apparatus 1690 is placed. The resonant signal is affected
by how magnetic the FeRh structure 1635 is in the middle of agarose
1680.
[0157] These gradient-echo images are shown in FIGS. 17A-17F. These
images are taken while maintaining the magnetic field magnitude at
4.7T. The FeRh structure 1635 is 99.9% purity FeRh disk having a
volume of 1 mm.sup.3. The images are taken through the center of
the disk 1635 at various temperatures as the disk 1635 is heated
and then cooled. In each of the images, a stable image feature 1781
is visible. This feature 1781 is produced by the thermometer 1681
next to the FeRh disk 1635. The thermometer 1681 is non-magnetic,
and thus, it does not exhibit any appreciable change in the images
as the magnetic field changes (due to the change in the
temperature) from FIG. 17A to FIG. 17F. The feature 1781 is
difficult to see in FIGS. 17C and 17D (but it is labeled to show
its location) because the signal from the FeRh disk 1635 overwhelms
it. FIG. 17G shows a width of the MRI signal 1782 (or image
artifact) created by signal loss due to the magnetic field
gradients from the FeRh disk 1635 as a function of the set-up
temperature.
[0158] Specifically, FIGS. 17A-17F show six representative
gradient-echo images (out of 52) of the effect of the FeRh mm-scale
disk 1635 on the surrounding agarose 1680 as the temperature of the
set-up is swept through physiologically relevant temperature range
(10-55.degree. C.) at the constant MRI magnetic field of 4.7 Tesla.
The image parameters are as follows: TR/TE=100/2.2 ms, FA=25
degrees, nominal resolution=0.46.times.0.46.times.1 mm,
FOV=60.0.times.60.0 mm. In chronological order, FIG. 17A shows the
gradient-echo image taken at a temperature of 25.degree. C.; FIG.
17B shows the gradient-echo image taken at a temperature of
45.degree. C.; FIG. 17C shows the gradient-echo image taken at a
temperature of 45.degree. C.; FIG. 17D shows the gradient-echo
image taken at a temperature of 35.degree. C.; FIG. 17E shows the
gradient-echo image taken at a temperature of 30.degree. C.; and
FIG. 17F shows the gradient-echo image taken at a temperature of
26.degree. C.
[0159] The demonstrated agarose image phase shift with concomitant
magnetic field change emanating from the magnetocaloric FeRh disk
1635 is seen in the increase of the MM signal 1782 around the
sample in FIGS. 17A-17F. As the magnetization data of FIG. 14B
dictates, the temperature increase drives the FeRh disk 1635 to
transition from the low-moment antiferromagnetic phase below the
transition temperature to the high-moment ferromagnetic phase above
the transition temperature and then back to the low-moment
antiferromagnetic phase as the FeRh disk 1635 is cooled. When the
magnetically manipulatable material 1635 goes to a magnetic state
(for example, increasing temperature for FeRh) from a non-magnetic
state, the surrounding substance (for example, agarose 1680), that
is, the substance around the magnetically manipulatable material
1635, sees both the background magnetic field produced by the
magnet 920 and the magnetic field produced from the now-magnetic
material (in this example, the FeRh in the disk 1635). That extra
field from the FeRh disk 1635 is non-uniform and in essence alters
the MRI signal 1782 around the FeRh to some distance, it puts it
out of detection range. This is why the gradient-echo image looks
much larger and darker as the magnetic field increases. It is not
that the FeRh disk 1635 is any bigger, it is that the FeRh disk
1635 changes its magnetic state, which in turn changes the MRI
signal of the surrounding substance 1680 and makes the image change
to a larger darker spot.
[0160] Loss of signal in the MM of FIGS. 17A-17F due to the
changing magnetic state of the magnetocaloric material closely
follows the magnetic properties that are shown in FIG. 14B. The
size of the region with signal dropout due to the high magnetic
field gradients approximately doubles in each dimension, a factor
of 8 in volume. This effect is plotted in FIG. 17G, which shows the
MM signal loss region size (in a linear dimension) as a function of
temperature. The image parameters are as follows: TR/TE=100/2.2 ms,
FA=25 degrees, nominal resolution=0.46.times.0.46.times.1 mm,
FOV=60.0.times.60.0 mm.
[0161] The clearly demonstrated phase shift with concomitant
magnetic field change is seen in the increase of the MRI signal
void. There was a larger hysteresis and lower apparent moment
increase in the MM data than in the magnetometer data, which may be
related to mechanical stress when cutting the material (the FeRh
disk 1635) to a smaller size. This hysteresis effect could be
viewed as a benefit, in that once a particle in the FeRh disk 1635
is turned "on" then it will remain on until removed from the
field.
[0162] In general, this result can be assumed to apply for the
magnetocaloric materials in the structure 135 when it is placed in
the magnet 120. When the magnetocaloric material is in a
non-magnetic state (for example, at a low temperature for FeRh or
at a high temperature for La--Fe--Si), the water surrounding the
structure 135 experiences just the MRI magnetic field supplied by
the magnet 120 on the order of Tesla (depending on the scanner
magnetic field). But when the magnetocaloric material goes to a
magnetic state (for example, at a high temperature for FeRh or at a
low temperature for La--Fe--Si), the water around the structure 135
experiences both the MRI scanner magnetic field (from the magnet
120) and the magnetic field from the now magnetic magnetocaloric
material in the structure 135. That extra field from the magnetic
magnetocaloric material is non-uniform and in essence alters the MM
water signal around the structure 135 to some distance, it puts it
out of detection range.
[0163] Switching protocols for using FeRh as the magnetically
manipulatable structure 135 are discussed next with reference to
FIGS. 18A-18C. A switching protocol describes the transition of the
magnetocaloric material in the structure 135 from the first
magnetic state to the second magnetic state. FIG. 18A shows the MRI
magnetic field at the value where the center of the first order
magnetic phase transition of the magnetocaloric material is at the
physiological temperature of 37.degree. C. Temporary heating and
cooling switches the magnetocaloric material between the MRI
visible (ON) and invisible (OFF) states. FIG. 18B shows the MRI
magnetic field is at the value where the center temperature of the
magnetocaloric material first order magnetic phase transition is
higher than the physiological temperature of 37.degree. C.
Temporary heating switches the magnetocaloric material to the MM
visible (ON) state while thermal relaxation to equilibrium
temperature brings the magnetocaloric material back to the MM
invisible (OFF) state. FIG. 18C shows the multiplexing of two
magnetocaloric materials that have phase transitions at two
different magnetic field values at the physiological temperature.
The two magnetocaloric materials are visible or invisible at
different magnetic fields and can therefore be differentiated in
images from different MRI scanners (in this example at 1T, 4T, and
7T).
[0164] As discussed above, FeRh is a suitable switchable and
tunable magnetocaloric material in the typical MM settings
(Tesla-scale magnetic fields) and in-vivo physiological
temperatures (around 37.degree. C.) through a very sharp first
order magnetic phase transition. FeRh is only one in a large
repertoire of magnetocaloric materials that have similar switching
characteristics under similar environmental conditions, where sharp
first order magnetic phase transition with a positive M vs. T slope
is observed at physiological temperatures and Tesla-scale magnetic
fields. Furthermore, there are many magnetocaloric materials where
the sharp first-order magnetic phase transitions can also have a
negative M vs. T slope at physiological temperatures and
Tesla-scale fields, or even a combination of sharp positive and
negative slopes, making magnetocaloric compounds even stronger
candidates as versatile materials for high differential contrast
switchable MM labels.
[0165] The switching protocols can be used for in-vivo MM settings.
The MRI contrast agent using FeRh can be reversibly switched by
thermal cycling of the entire sample set-up over the
physiologically relevant temperature range. Other potential
engineering solutions to magnetocaloric MRI label switching include
heating by MRI compatible focused ultrasound or high-frequency
inductive heating, cooling by MRI compatible thermo-electric
coolers, or magnetocaloric material switching by adding or
subtracting to the main magnetic field of the MRI (in the simplest
version this can be accomplished by temporarily removing the sample
from the MRI bore).
[0166] When considering such MRI label switching solutions,
magneto-thermal properties of the magnetocaloric material are also
considered, especially the location of the first order magnetic
phase transition of the magnetocaloric material. FIGS. 18A-18C
schematically describe specific examples. In FIG. 18A, the MM label
has two stable magnetic states (indicated by the solid black dots)
at 37.degree. C. (310K). This example is well represented by the
99.9% purity FeRh magnetocaloric material at 5 Tesla, as shown in
FIG. 14B. In the low magnetic moment state the magnetocaloric
material is MRI invisible (Label OFF). The magnetocaloric material
can be switched on by temporarily raising its temperature by few
degrees C. (approximately .DELTA.T=5.degree. C. for our 99.9%
purity FeRh magnetocaloric material at 5 Tesla shown in FIG. 14B)
through application of a heating pulse (by any of the above listed
potential methods). Once the magnetocaloric material is thermally
relaxed back to the equilibrium temperature of 37.degree. C., it
remains in the high magnetic moment state and is MRI visible (Label
ON). It can be switched off again by active cooling where the
temperature of the magnetocaloric material is temporarily lowered.
Once the magnetocaloric material relaxes back to the equilibrium
temperature of 37.degree. C., it will be in the low magnetic moment
state and again MRI invisible (Label OFF). This is also the
procedure performed for obtaining the gradient-echo images as
described in FIGS. 17A-17F.
[0167] The second possibility is described in FIG. 18B. In this
case the magnetocaloric material has only one stable magnetic state
(indicated by the solid black dot) at 37.degree. C. (310K). This
example is well represented by 99.9% purity FeRh magnetocaloric
material at 3 Tesla, as shown in FIG. 14B. In this low magnetic
moment state the magnetocaloric material is MRI invisible (Label
OFF). The magnetocaloric material can be temporarily switched on by
raising its temperature through application of a larger heat pulse
than was described in FIG. 18A since higher temperature change is
required to take the magnetocaloric material through the first
order magnetic phase transition (In the case of our 99.9% purity
FeRh at 3T as shown in FIG. 14B, it would take approximately
.DELTA.T=20.degree. C. to switch the magnetocaloric material). The
magnetocaloric material remains MRI visible (Label ON) in the high
magnetic moment state as long as the temperature of the
magnetocaloric material is above the phase transition temperature.
As the magnetocaloric material thermally relaxes back to the
equilibrium temperature of 37.degree. C., it automatically goes
back through the phase transition into a low magnetic moment state
and becomes MM invisible again (Label OFF). The advantage of this
configuration is that active cooling is not required for switching
the magnetocaloric material into the MM invisible OFF state, while
the disadvantage is that the higher temperature increase is
required to temporarily switch the label into the MM visible ON
state.
[0168] Another feature of MRI switchable labels brought about by
the variety of magneto-thermal properties of magnetocaloric
materials is the possibility of multiplexed labels made MRI visible
or invisible at different magnetic field or temperature values by
appropriate materials science design. FIG. 18C describes the
possibility of two switchable MRI labels that can be differentiated
in images from MRI scanners operating at different magnetic field
values. Label 1 has a first order magnetic phase transition at 2
Tesla and is well represented by the 99% purity FeRh magnetocaloric
material at 27.degree. C. (300K) shown in FIG. 15A. Label 2 has a
first order magnetic phase transition at 6 Tesla and is well
represented by the 99.9% purity FeRh magnetocaloric material at
27.degree. C. (300K) shown in FIG. 15B. In a 1T MRI scanner, both
of these labels would be in the low magnetic moment state below
their respective first order magnetic phase transition temperatures
and therefore invisible in the MM (both labels OFF). In a 4T MRI
scanner, Label 1 would be in the high magnetic moment state above
its magnetic phase transition temperature and therefore MM visible
(Label 1 ON), while Label 2 would still be in the low magnetic
moment state below its magnetic phase transition temperature and
therefore still MRI invisible (Label 2 OFF). Finally, in a 7T MM
scanner, both of these labels would be in the high magnetic moment
states above their respective magnetic phase transition
temperatures and therefore MM visible (both labels ON). Images from
these MM scanners with different operating DC magnetic fields would
readily differentiate the two labels.
[0169] Referring to FIGS. 19A and 19B, two different magnetically
manipulatable materials are shown that function similarly to the
examples shown in FIGS. 6A and 6B, respectively. In FIG. 19A, the
magnetically manipulatable material is Fe--La--Si, while in FIG.
19B, the magnetically manipulatable material is 99% purity FeRh.
FIG. 19A is a graph of the magnetic state of Fe--La--Si versus
temperature T within the sample 115, while maintaining the sample
115 at a constant magnetic field of 1 T. As shown in this graph,
Fe--La--Si transitions from a magnetic to a non-magnetic state with
a rise in the temperature T. FIG. 19B is a graph of the magnetic
state of 99% purity FeRh versus temperature T within the sample
115, while maintaining the sample 115 at a constant magnetic field
of 1 T. As shown in this graph, FeRh transitions from a
non-magnetic to a magnetic state with a rise in the temperature
T.
[0170] Referring to FIG. 20, a procedure 2000 is performed by the
apparatus 200 for using the magnetic apparatus 205 and the
magnetically manipulatable structure 235 to control, alter, or
operate on the sample 215. For example, the structure 235 can
include the magnetically manipulatable materials 236, the magnetic
apparatus 205 can be an MM machine, and the materials 236 can act
as one or more tunable and switchable labels in the MRI machine
205.
[0171] The procedure 2000 includes receiving the sample 215 in the
sample volume 210 defined by the magnetic apparatus 205 and the
magnet 220 (2005). The sample 215 can be placed inside the magnet
220 using any suitable technique that is used in MRI machines. The
sample 215 can be a whole living organism, or it can be a portion
or a region of a living organism. The magnetically manipulatable
structure 235 and the material 236 are prepared within the sample
215 (2010). For example, the structure 235 can be embedded within
the sample 215 using the injection apparatus 260 and this can occur
prior to or after the sample 215 is placed inside the magnet
220.
[0172] The magnetic field having the magnitude B is created in the
sample 215 (2015). For example, the control system 240 can send a
signal to the energy supply 225 to provide current to the
electrically conductive wire coils of the magnet 220. The magnitude
B of the magnetic field is generally greater than 0.5 Tesla and can
be in a range of 1-20 Tesla.
[0173] A property associated with the sample 215 is changed while
generally maintaining the magnetic field magnitude B constant in
the sample 215 (2020). The property that is changed (2020) can be
the magnetic field or a temperature or both the magnetic field and
the temperature of the sample 215. If the property that is changed
is the magnetic field, then the change in the magnetic field is
substantially smaller than the magnitude B of the field that is
held constant. The change in magnetic field is at least an order of
magnitude smaller than the magnitude B. Similarly, if the overall
temperature of the sample 215 is between about 270-370 K, and the
property to be changed (2020) is the temperature, then the change
in the temperature is substantially less than the overall
temperature of the sample 215. For example, the temperature change
can be about 10-40 K. The change in the property (2020) can be
affected by the sample property scanning system 245, as discussed
above.
[0174] Because the magnetically manipulatable structure 235
includes magnetically manipulatable materials 236, the change in
the property (2020) causes the magnetically manipulatable materials
236 to transition from a first magnetic state to a second magnetic
state, and this transition causes a change in the sample 215 near
to the structure 235. This change in the sample 215 is detected
(2025). This means that the structure 235 can be turned on and off
by the procedure 2000 and has the effect that it can be used as a
high-contrast tunable and switchable label for MRI machines 205.
The structure 235 can therefore be used as an MRI contrast agent or
a sensor because of these properties. Thus, the change in the
magnetization of the magnetically manipulatable materials 236 of
the structure 235 can be detected by the apparatus 200 by observing
the effect the change has on the water or biological tissue
surrounding the materials 236.
[0175] Referring to FIG. 21, a procedure 2100 is performed by the
apparatus 900 for actuating (for example, activating and
de-activating) a biological construct (which can be the
thermally-sensitive biological construct 930) within a sample 915.
The sample 915 is received in the actuation volume 910 defined by
the magnet 920 of the magnetic apparatus 905 (2105). The
magnetically manipulatable structure 935 is physically (for
example, thermally) coupled with the biological construct within
the sample 915 (2110) such that the biological construct changes
its status in response to a change in property of the magnetically
manipulatable structure 935. Thus, if the physical coupling is a
thermal coupling and the biological construct is a
thermally-sensitive biological construct 930, then the
thermally-sensitive biological construct 930 changes its status in
response to a change in a temperature of the magnetically
manipulatable structure 935.
[0176] The magnetic field having the magnitude B is created in the
sample 915 (2115). For example, the control system 940 can send a
signal to the energy supply 925 to provide current to the
electrically conductive wire coils of the magnet 920. The magnitude
B of the magnetic field is generally greater than 0.5 Tesla and can
be in a range of 1-20 Tesla.
[0177] A characteristic within the sample 915 is changed (2120) For
example, the characteristic of the sample 915 that is changed
(2120) is the magnetic field within the sample, 915. The magnetic
field within the sample 915 can be changed by changing a DC current
supplied to the magnet 920. The change in the magnetic field is
substantially smaller than the magnitude B of the field that is
held constant. The change in magnetic field is at least an order of
magnitude smaller than the magnitude B. The change in the
characteristic within the sample 915 (2120) can be affected by the
sample property scanning system 245, as discussed above.
[0178] The change in the characteristic (such as the magnetic
field) (2120) causes the property (such as the temperature) of the
magnetically manipulatable material 936i to change, and this causes
a change in a status of the biological construct (2125). The change
to the status of the biological construct (2125) can occur without
causing a change in the status of other materials within the sample
915. For example, the change in the magnetic field (212) causes a
change in the temperature of the magnetically manipulatable
material 936i, and this causes a change in the status of the
thermally-sensitive biological construct 930.
* * * * *