WO2024107310A1 - Commande par retour d'informations de température guidée par image pour réchauffement magnétique sans dommage et récupération de tissu cryoconservé - Google Patents
Commande par retour d'informations de température guidée par image pour réchauffement magnétique sans dommage et récupération de tissu cryoconservé Download PDFInfo
- Publication number
- WO2024107310A1 WO2024107310A1 PCT/US2023/035675 US2023035675W WO2024107310A1 WO 2024107310 A1 WO2024107310 A1 WO 2024107310A1 US 2023035675 W US2023035675 W US 2023035675W WO 2024107310 A1 WO2024107310 A1 WO 2024107310A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- biological tissue
- temperature
- vivo organ
- magnetic
- magnetic field
- Prior art date
Links
- 230000005291 magnetic effect Effects 0.000 title claims abstract description 94
- 230000006378 damage Effects 0.000 title description 12
- 238000011084 recovery Methods 0.000 title description 4
- 210000000056 organ Anatomy 0.000 claims abstract description 140
- 238000000034 method Methods 0.000 claims abstract description 89
- 239000006249 magnetic particle Substances 0.000 claims abstract description 80
- 239000000203 mixture Substances 0.000 claims abstract description 54
- 238000003384 imaging method Methods 0.000 claims abstract description 49
- 238000010792 warming Methods 0.000 claims abstract description 40
- 238000004321 preservation Methods 0.000 claims abstract description 36
- 239000000084 colloidal system Substances 0.000 claims abstract description 19
- 238000001816 cooling Methods 0.000 claims abstract description 18
- 238000009826 distribution Methods 0.000 claims abstract description 14
- 238000005094 computer simulation Methods 0.000 claims abstract description 10
- 238000013170 computed tomography imaging Methods 0.000 claims abstract description 5
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 51
- 239000002577 cryoprotective agent Substances 0.000 claims description 30
- 239000000523 sample Substances 0.000 claims description 25
- 238000004088 simulation Methods 0.000 claims description 24
- 238000009472 formulation Methods 0.000 claims description 17
- 239000002245 particle Substances 0.000 claims description 17
- 230000003044 adaptive effect Effects 0.000 claims description 14
- 238000005336 cracking Methods 0.000 claims description 13
- 230000004807 localization Effects 0.000 claims description 12
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 9
- 238000012546 transfer Methods 0.000 claims description 9
- 238000002425 crystallisation Methods 0.000 claims description 8
- 238000005457 optimization Methods 0.000 claims description 8
- 230000008025 crystallization Effects 0.000 claims description 7
- 230000005415 magnetization Effects 0.000 claims description 6
- 238000012544 monitoring process Methods 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 230000000903 blocking effect Effects 0.000 claims description 5
- 230000002349 favourable effect Effects 0.000 claims description 5
- 229910052742 iron Inorganic materials 0.000 claims description 5
- 230000002123 temporal effect Effects 0.000 claims description 4
- 108010053481 Antifreeze Proteins Proteins 0.000 claims description 3
- 238000012805 post-processing Methods 0.000 claims description 3
- 235000000346 sugar Nutrition 0.000 claims description 3
- 150000008163 sugars Chemical class 0.000 claims description 3
- 230000000007 visual effect Effects 0.000 claims description 3
- 229910001218 Gallium arsenide Inorganic materials 0.000 claims description 2
- 230000001939 inductive effect Effects 0.000 claims description 2
- 210000001519 tissue Anatomy 0.000 description 91
- 210000004185 liver Anatomy 0.000 description 26
- 239000002122 magnetic nanoparticle Substances 0.000 description 25
- 230000008569 process Effects 0.000 description 16
- 238000010438 heat treatment Methods 0.000 description 13
- 238000003860 storage Methods 0.000 description 13
- 238000002054 transplantation Methods 0.000 description 11
- 239000000463 material Substances 0.000 description 10
- 238000005138 cryopreservation Methods 0.000 description 8
- 238000005516 engineering process Methods 0.000 description 8
- 238000002595 magnetic resonance imaging Methods 0.000 description 7
- 241000283984 Rodentia Species 0.000 description 6
- 230000010412 perfusion Effects 0.000 description 5
- 229910000859 α-Fe Inorganic materials 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 210000003494 hepatocyte Anatomy 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 239000000082 organ preservation Substances 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 230000002631 hypothermal effect Effects 0.000 description 3
- 230000006910 ice nucleation Effects 0.000 description 3
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 3
- 230000008520 organization Effects 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000000700 radioactive tracer Substances 0.000 description 3
- 230000011218 segmentation Effects 0.000 description 3
- 210000005166 vasculature Anatomy 0.000 description 3
- JBRZTFJDHDCESZ-UHFFFAOYSA-N AsGa Chemical compound [As]#[Ga] JBRZTFJDHDCESZ-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000009529 body temperature measurement Methods 0.000 description 2
- 238000004422 calculation algorithm Methods 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229910017052 cobalt Inorganic materials 0.000 description 2
- 239000010941 cobalt Substances 0.000 description 2
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 210000005161 hepatic lobe Anatomy 0.000 description 2
- 238000010191 image analysis Methods 0.000 description 2
- 239000000696 magnetic material Substances 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000013341 scale-up Methods 0.000 description 2
- 230000000930 thermomechanical effect Effects 0.000 description 2
- 238000004861 thermometry Methods 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- 238000012795 verification Methods 0.000 description 2
- 206010057573 Chronic hepatic failure Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 208000010334 End Stage Liver Disease Diseases 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- 229910002546 FeCo Inorganic materials 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- 206010020843 Hyperthermia Diseases 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 1
- 229910052772 Samarium Inorganic materials 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000005275 alloying Methods 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 238000013473 artificial intelligence Methods 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- OWBTYPJTUOEWEK-UHFFFAOYSA-N butane-2,3-diol Chemical compound CC(O)C(C)O OWBTYPJTUOEWEK-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 208000011444 chronic liver failure Diseases 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000002059 diagnostic imaging Methods 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 208000010706 fatty liver disease Diseases 0.000 description 1
- 230000005293 ferrimagnetic effect Effects 0.000 description 1
- 230000005294 ferromagnetic effect Effects 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 238000009499 grossing Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 210000002767 hepatic artery Anatomy 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 238000003709 image segmentation Methods 0.000 description 1
- 238000001095 inductively coupled plasma mass spectrometry Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000010801 machine learning Methods 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000010603 microCT Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000008450 motivation Effects 0.000 description 1
- 239000002057 nanoflower Substances 0.000 description 1
- 229940031182 nanoparticles iron oxide Drugs 0.000 description 1
- 239000002073 nanorod Substances 0.000 description 1
- 239000002070 nanowire Substances 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 238000013021 overheating Methods 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 231100000620 pharmacotoxicology Toxicity 0.000 description 1
- 210000003240 portal vein Anatomy 0.000 description 1
- 238000011028 process validation Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- KZUNJOHGWZRPMI-UHFFFAOYSA-N samarium atom Chemical compound [Sm] KZUNJOHGWZRPMI-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 238000004017 vitrification Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0205—Chemical aspects
- A01N1/021—Preservation or perfusion media, liquids, solids or gases used in the preservation of cells, tissue, organs or bodily fluids
- A01N1/0221—Freeze-process protecting agents, i.e. substances protecting cells from effects of the physical process, e.g. cryoprotectants, osmolarity regulators like oncotic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
- A61B5/0515—Magnetic particle imaging
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
- A61B5/055—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
Definitions
- the present teachings relate generally to medical imaging and, more particularly, to image guided temperature control related to preservation to preserved tissue.
- liver disease including cancer
- Liver transplantation remains the best treatment option to extend life expectancy and quality of life, and is often the sole treatment option for many patients.
- Developing technologies and methods to extend organ storage times can quickly alleviate this gap and enable transportation of organs for transplantation over greater distances.
- these technologies could be extended to hepatic subsystems, such as hepatocytes, precision cut liver slices, liver lobes, and extended criteria donors, for example, fatty livers, potentially having a tremendous impact on tissue regeneration, liver pathophysiology and pharmacotoxicology research.
- Cryopreservation of cells and tissues has shown tremendous potential and success towards long-term storage. Organ and tissue storage time increases at cryogenic temperatures because cellular metabolic activity and molecular diffusion are dramatically reduced. Cryopreservation technology can be extended to whole vascularized organs through a process called vitrification, such as rapid cooling of organs, perfused with cryoprotectants, to cryogenic temperatures (-150°C), where they can be stored in a glassy state without damage from ice. However, before these organs can be recovered for transplantation they need to be rewarmed rapidly and uniformly from cryogenic temperatures, which remains a challenge, especially at the scale of whole organs.
- warming rates required to prevent damage from ice-crystallization are typically an order of magnitude higher ( ⁇ > 100 °C/min) than cooling rates of cryoprotectants used for organ preservation. Additionally, the organ needs to be rewarmed uniformly to minimize thermal gradients to avoid cracking arising from thermomechanical stresses.
- One general aspect of the present disclosure includes a method for preserving and recovering biological tissue.
- the method includes perfusing an ex vivo organ with a biological tissue preservation composition or mixture which may include a magnet-responsive colloid, scanning the ex vivo organ using magnetic particle imaging, cooling the perfused ex vivo organ to a first temperature.
- the method also includes scanning an ex vivo organ using magnetic particle imaging to generate one or more images representing a distribution of magnet-responsive colloid within the ex vivo organ.
- the method also includes co-registering the magnetic particle imaging with MRI and/or CT imaging of the biological tissue.
- the method also includes generating 3D computational models for the biological tissue from coregistered images.
- the method also includes applying an effective alternating magnetic field to the ex vivo organ using a magnetic field coil that is external to the ex vivo organ.
- the method also includes warming the ex vivo organ from the first temperature to a second temperature.
- Implementations of the method for preserving and recovering biological tissue may include where the biological tissue preservation composition may include organic solvents including ethylene glycol, sugars, antifreeze proteins, a magnet-responsive colloid, or a combination thereof.
- the ethylene glycol is present in the biological tissue preservation composition in an amount of from about 10 % to about 50% based on a total weight of the biological tissue preservation composition.
- the magnet-responsive colloid may include a plurality of magnetic particles having a particle size of from about 1 nm to about 10 microns.
- the method for preserving and recovering biological tissue may include storing the ex vivo organ at or below the first temperature.
- the method for preserving and recovering biological tissue may include, maintaining the ex vivo organ at or below the first temperature, and transporting the ex vivo organ from a first geographical location to a second geographical location.
- the perfused ex vivo organ is cooled to the first temperature at a rate of from about 0.5°C/min to about 20°C /min.
- the perfused ex vivo organ is warmed to the second temperature at a rate greater than 50°C /min.
- the first temperature is from about 0°C to about -150°C.
- the second temperature is from about 0°C to about 40°C.
- the method for preserving and recovering biological tissue may include, performing one or more finite element modeling-based simulations of coupled electromagnetic and heat transfer in 3D models of the biological tissue using the one or more generated images, and inputting optimization results of the one or more simulations including proportional, integral and derivative gains into a multi-input multi-output (MIMO) adaptive temperature feedback control system to control one or more parameters of the magnetic field.
- the one or more parameters of the magnetic field may include frequency, amplitude, power, spatial and temporal localization of the effective alternating magnetic field region relative to one or more biological tissue boundaries or a combination thereof.
- the method for preserving and recovering biological tissue may include monitoring temperature of the ex vivo organ while applying the magnetic field, and modulating an amplitude, power or spatiotemporal localization of the magnetic field supplied by the magnetic coil to control a rate of warming of the ex vivo organ.
- the magnetic field coil supplies an alternating magnetic field to the ex vivo organ.
- the method for preserving and recovering biological tissue may include cooling the perfused ex vivo organ to a first temperature prior to scanning the ex vivo organ using magnetic particle imaging.
- the method for preserving and recovering biological tissue may include cooling the perfused ex vivo organ to a first temperature after scanning the ex vivo organ using magnetic particle imaging.
- the magnet-responsive colloid may include magnetic particles have a particle size of from about 1 nm to about 10 microns.
- a biological tissue preservation composition includes a cryoprotectant formulation, and a plurality of magnetic particles dispersed within the cryoprotectant formulation.
- Implementations of the biological tissue preservation composition may include where the cryoprotectant formulation includes ethylene glycol.
- the ethylene glycol is present in an amount of from about 10 % to about 50% based on a total weight of the biological tissue preservation composition.
- the plurality of magnetic particles may include iron.
- the plurality of magnetic particles have a particle size of from about 1 nm to about 10 microns.
- the plurality of magnetic particles are present in an amount of from about 0.0 1 % to about 10% based on a total weight of the biological tissue preservation composition.
- the plurality of magnetic particles have favorable magnetic, thermal and colloidal properties including saturation magnetization, coercivity, hysteresis area, high specific loss power, high magnetic particle imaging intensity and resolution, blocking temperature, curie temperature, colloidal stability in the temperature range of -150°C to 40°C.
- a system for recovering biological tissue includes a radiofrequency (100-440 khz) alternating magnetic field coil, de gradient field coils for spatiotemporal localization of an effective alternating magnetic field region within the biological tissue volume.
- the system also includes a magnetic particle imaging scanner.
- the system also includes a multi-input multi-output adaptive feedback control device connected to an input of an alternating magnetic frequency coil.
- Implementations of the system for recovering biological tissue may include where the feedback control device further includes a temperature probe.
- the temperature probe is a fiberoptic temperature probe having one or more gallium arsenide (GaAs) sensors along a length of the temperature probe.
- GaAs gallium arsenide
- the output from the magnetic particle imaging scanner may include imaging data, processed in a separate workstation to generate 3D models of the biological tissue and particle distribution as inputs to finite element modeling-based simulations.
- the output from the magnetic particle imaging scanner may include a visual display, processed separately in a workstation for post-processing, 3D model generation, computer simulation, or a combination thereof.
- the radiofrequency alternating magnetic field coil is configured to provide heat to a biological tissue sample.
- the biological tissue sample is perfused with a biological tissue preservation composition.
- the biological tissue preservation composition may include, a cryoprotectant formulation, and a magnetic particle dispersed within the cryoprotectant formulation.
- the cryoprotectant formulation may include organic solvents including ethylene glycol.
- the ethylene glycol is present in an amount of from about 10 % to about 50% based on a total weight of the biological tissue preservation composition.
- the magnetic particle may include ferrite-based particles.
- the magnetic particle has a particle size of from about 1 nm to about 10 microns.
- the magnetic particle is present in an amount of from about 0.01 % to about 10% based on a total weight of the biological tissue preservation composition.
- the magnetic particle has favorable magnetic, thermal and colloidal properties including saturation magnetization, coercivity, hysteresis area, high specific loss power, high magnetic particle imaging intensity and resolution, blocking temperature, curie temperature, colloidal stability in the temperature range of -150°C to 40°C.
- FIG. 1 is a schematic illustrating a system for magnetic-based image-guided magnetic warming of a cryopreserved organ using temperature-feedback control, in accordance with the present disclosure.
- FIG. 2 is a block diagram illustrating a portion of a process for a feedback-controlled magnetic rewarming system, in accordance with the present disclosure.
- FIG. 3 is a flowchart illustrating a method for preserving and recovering biological tissue, in accordance with the present disclosure.
- Issues associated with preserving organs can include those related to the volume of the organs as they scale. For example, ice crystals are a primary issue with this system, measurement, and method as described herein. Temperature gradients across the volume when using typical warming procedures in a “bath” can result in cracking. This includes issues associated with internal heating as localized within the blood vessels. Therefore, an additional feedback control algorithm is needed to modulate the power.
- a system or device is provided that integrates these functions as well as the method of cryopreservation with the use of magnetic particle -based warming. Imaging and feedback control are integral components of the measurement and rewarming system.
- the current clinical standard for organ preservation is storage on ice, in which a heart may survive for six hours, a liver may survive for approximately 12 hours, or a kidney may survive for approximately 18 hours. Under these conditions, up to 20% of organs may be discarded due to issues with storage and/or transportation. Examples of the present disclosure provide a movement from an emergency driven system to one unconstrained by time or geography. By adopting cryopreservation, a reduction of metabolic activity can result, slowing down time for degradation and other issues associated with organ preservation and storage. While storing at or below 4 °C, in the range of ice storage, ice crystals can form.
- CPA cryoprotecting agents
- Rapid cooling can lock an organ perfused with CPAs into a glassy state, and therefore be stored for months, as there is no molecular diffusion.
- An additional challenge is subsequent rewarming of the ex vivo organ, as it adds much higher constraints to avoid ice crystals and cracking. Convective rewarming cannot achieve the required rate to avoid the formation of ice.
- Magnetic particle heating is based on hysteresis of the plurality of magnetic particles when subjected to an alternating magnetic field. Magnetic field (AC) direction changes and the moments of perfused magnetic nanoparticles can allow a more controlled manipulation of the temperature of the MNPs and therefore the re warming temperature, as well as the rate of rewarming. By contrast, a constant magnetic field could cause non-uniformity in re warming.
- the present disclosure provides for the development of a scalable automated rewarming method for recovering intact cryopreserved organs, in certain examples, livers, for transplantation using rapid and uniform magnetic rewarming based on imaging-guided computational planning and real-time temperature feedback-control.
- Methods and systems of the present would prevent physical damage of the organ due to ice nucleation, and tissue cracking from thermal gradients during recovery from a cryopreserved state.
- the motivation for such a scalable organ preservation technology is that storage at lower than hypothermic temperatures (0-4°C) can increase storage times of transplantable organs beyond current limits, for example, 12 hours for livers on ice, and would therefore, increase the supply of transplantable organs to reduce waiting lists.
- FIG. 1 is a schematic illustrating a system for magnetic-based image-guided magnetic warming of a cryopreserved organ using temperature-feedback control, in accordance with the present disclosure.
- FIG. 1 illustrates a system for magnetic-based magnetic warming of a cryopreserved organ 100, also referred to as a system for recovering biological tissue 100 including a radiofrequency (100-440 kHz) alternating magnetic field coil 116, which may further include DC gradient field coils for spatiotemporal localization of the effective alternating magnetic field region within a biological tissue 106 volume a magnetic particle imaging (MPI) scanner 114.
- An MPI scanner or imager can detects a tracer material within the biological tissue 106.
- the technology detects only the tracer material does not see or interact with the biological tissue 106.
- the MPI scanner provides a strong magnetic field gradient inside the imaging volume by a main magnet. With the magnetic particle imaging (MPI) scanner 114, an initial set of images of a biological tissue 106 sample is recorded.
- the biological tissue 106 as shown, is a cryopreserved liver held in a container for organ storage 108, where a temperature monitor 110 is used to monitor the temperature at various places within the use of the system 100 and while practicing the method of preserving and recovering biological tissue 106.
- the temperature probe 110 can include a fiberoptic temperature probe having one or more GaAs sensors along the probe length.
- Alternate realtime temperature measurements can include 3D thermometry from the MNPs in MPI imaging which utilizes temperature-dependent magnetic relaxation dynamics of the MNPs. It should be noted that rewarming an ex vivo organ using feedback temperature control is a feature provided by the methods and systems of the present disclosure. In certain examples, it may be considered that an effective alternating magnetic field can be more precisely controlled using a feedback control system such as those described herein to deliver, when subjecting magnetic particles possessing a hysteresis effect heating capability to produce the well- controlled heating necessary for ex vivo organ rewarming.
- the container for organ storage 108 is placed in a carrier 112 that is introduced into the image scanner 114 to generate image data 122.
- the biological tissue sample 106 Prior to imaging, the biological tissue sample 106 is perfused with a biological tissue preservation composition including a cryoprotectant formulation 104 and a plurality of magnetic particles 102 dispersed within the cryoprotectant formulation 104.
- the cryoprotectant formulation 102 includes organic solvents including ethylene glycol, for example.
- organic solvents used in cryoprotectant formulations which can be used herein include propylene glycol, formamide, dimethyl sulfoxide (DMSO), polyethylene glycol (PEG), 2,3 butanediol, N-methylformamide, polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), commercially available CPAs including M22 (21st Century Medicine Inc), or combinations thereof.
- the solvent or ethylene glycol is present in an amount of from about 10 % to about 50%, or from about 10% to about 40%, or from about 30% to about 40%, based on a total weight of the biological tissue preservation composition 104.
- the magnetic particles 102 can include, but are not limited to ferrite-based particles.
- Illustrative magnetic particles can include different (i) compositions - ferromagnetic Co, Ni, Fe, FeCo nanoparticles, ferrimagnetic - iron oxide, cobalt ferrite, manganese ferrite, (ii) shapes - spherical, nanowires/nanorods, nanoflowers (iii) sizes - nano to micro scale limited by capillary diameter including commercially available microspheres with embedded iron oxide nanoparticles, (iv) different coatings - PEG, starch, dextran, and certain FDA approved lipid formulations including magnetic cores, or combinations thereof.
- the magnetic particle 102 has a particle size of from about 1 nm to about 10 microns, or from about 10 nm to about 1 micron, or from about 50 nm to about 100 nm. In certain examples, the particle size of the magnetic particle 102 may be limited by vessel dimensions in the biological tissue sample 106 intended for cryopreservation. The magnetic particle 102 is present in an amount of from about 0.01 % to about 10% based on a total weight of the biological tissue preservation composition.
- the magnetic particle 102 has favorable magnetic, thermal and colloidal properties including saturation magnetization, coercivity, hysteresis area, high specific loss power, high magnetic particle imaging intensity and resolution, blocking temperature, curie temperature, and colloidal stability in the temperature range of - 150°C to 40°C.
- the cryoprotectant formulation can include ethylene glycol, wherein the ethylene glycol is present in an amount of from about 10 % to about 50% based on a total weight of the biological tissue preservation composition.
- Illustrative examples include where the magnetic particle comprises iron, or having a particle size of from about 1 nm to about 10 microns, or where the magnetic particle is present in an amount of from about 0.0 1 % to about 10% based on a total weight of the biological tissue preservation composition, or a combination thereof.
- Further properties of the magnetic particle can include where the magnetic particle in the biological tissue preservation composition has favorable magnetic, thermal and colloidal properties including saturation magnetization, coercivity, hysteresis area, high specific loss power, high magnetic particle imaging intensity and resolution, blocking temperature, curie temperature, colloidal stability in the temperature range of -150°C to 40°C, or a combination thereof.
- any magnet-responsive colloid would be applicable to the systems and methods of the present disclosure, including the aforementioned nanoparticles.
- other magnetic materials such as cobalt, nickel, samarium, and the like would be applicable in addition to ferrite-based materials.
- Curie temperature control can be an alternate strategy for rewarming applications, which by alloying with different magnetic materials having varied Curie temperatures, can provide further options for Curie temperature control of heating or warming in order to prevent overheating.
- the cryopreserved biological tissue 106 is frozen until such time as the biological tissue 106 is necessary for transplantation or for other purposes.
- a multi -input multi -output adaptive feedback control device 118 connected to an input of the alternating magnetic frequency coil 116 is used as part of the system for recovering biological tissue 100.
- the radiofrequency alternating magnetic field coil 116 is configured to provide heat to the biological tissue sample 106 during the rewarming process.
- the heating of the plurality of magnetic particles is based on hysteresis of the plurality of magnetic particles when subjected to an alternating magnetic field and accomplished by a coupling of the effective alternating magnetic field with the magnet-responsive colloid or a plurality of magnetic particles.
- the alternating magnetic frequency coil 116 is connected electrically and by a suitable data transmission connection to a feedback control unit 118 and image guided feedback module 120, illustrated as a monitor, configured for artificial intelligence (Al)-based 3D segmentation 122, segmented image meshing 124, and finite element predictive modeling 126.
- the feedback control device 118 also includes a temperature probe 110 for monitoring the rewarming process for the biological tissue 106.
- the output from the magnetic particle imaging scanner 114 includes initial and in-process imaging data 122, processed in a separate workstation to generate 3D models 126 of the biological tissue 106 and evaluate magnetic particle 102 distribution as inputs to finite element mode ling -based simulations 126, in some examples with the use of meshing 124 of the 3D models 126 based on the imaging data 122.
- the output from the magnetic particle imaging scanner 114 further includes a visual display 120 and provides an image guided feedback model, processed separately in a workstation for post-processing, 3D model generation, computer simulation, or a combination thereof.
- a rodent liver will be perfused, ex vivo, with cryoprotectants (CPAs) and magnetic nanoparticles (MNPs) followed by an application of the application of magnetic particle imaging (MPI) to determine the distribution of the nano-heaters.
- CPAs cryoprotectants
- MNPs magnetic nanoparticles
- MPI magnetic particle imaging
- This warming process can be considered automated warming, as the warming uses real-time, in-process feedback from temperature data, along with experimental data and computer simulations, as inputs to guide the system to warm the organs from a first temperature to a second temperature.
- the warming can be accomplished using an automated feedback control.
- MNP magnetic nanoparticles
- CPF cryoprotectant agent
- MNPs provide a tracer yielding high spatial resolution of the MNPs with quantitative MNP concentration within the organ without damage when MPI is used.
- pCT micro computed tomography
- MRI magnetic resonance imaging
- Ethylene glycol (EG)-based CPAs can be used for perfusion, as they possess documented thermal properties, physically attainable cooling and warming rates to avoid ice crystallization, and have shown biocompatibility with hepatocytes, spheroids and livers.
- a Momentum MPI scanner, and compatible hyperthermia platform, HYPER prototype (Ivkov lab), capable of integration with MPI, are unique capabilities that allow truly integrated imaging -guided heat treatments.
- the MPI-HYPER combination can be used for rewarming cryopreserved tissues, providing a translational and scalable solution to this application.
- MRI images of the liver can be co-registered with MPI, to determine the MNP distribution relative to anatomical structures, which are used in the analysis in MPI- guided electromagnetic (EM) and heat transfer simulations of rewarming to optimize AMF amplitude and power feedback control protocols.
- EM MPI- guided electromagnetic
- the minimum cooling rate (critical cooling rate, CCR -l°C/min) and rewarming rate (critical warming rate, CWR 50°C/min), can be specified to avoid ice crystallization, based on the thermal properties and documented differential scanning calorimetry (DSC) measurements of the CPA used, in certain examples, 40% EG.
- Upper thresholds can also be placed on thermal gradients, for example a dT/dr ⁇ 5°C/cm, to avoid cracking, based on the thermomechanical properties of 40% EG in glassy state.
- MPI and MRI co-registered liver images are imported into Mimics Medical 24.0 (Materialise) for segmentation and meshing.
- the segmentation of major hepatic blood vessels, such as portal vein, hepatic artery, major blood vessels, and the sinusoids can be accomplished using voxel intensity-based thresholding. Meshing and smoothing of the 3D liver and vasculature are optimized using Materialise 3-Matic software. The smoothed and meshed 3D liver data is exported to COMSOL Multiphysics for coupled EM and heat transfer simulations. For scaling the image contrast from the MNPs to iron concentration (cFe), MPI signal-intensity calibration is performed against ICP-MS Fe standards. An SLP value, based on experimental measurement of SLP of Synomag MNPs in CPA, will be attributed to the MNP heat sources in the vasculature within the model. Additionally, Joule heating from eddy-currents will be accounted for by defining the temperature-dependent electrical conductivity of the CPA-perfused liver tissue.
- Convective boundary conditions are assigned to the container holding the vitrified liver.
- Proportional-integral-derivative (PID)-based feedback control and machine learning methods are employed to maintain warming rates above the critical warming rate (>CWR) and dT/dr below ( ⁇ ) a threshold gradient.
- the Johnson-Avrami model can be used to then quantitively predict the volume fraction of ice crystallization during rewarming, and generate a 3D strain map to quantify the probability of cracking.
- Process validation and verification are performed experimentally on containers containing CPA only in a temperature ranging from - 150°C to 0°C. Finally, application of the rewarming methods resulting from validated simulations to vitrified rodent livers is done.
- Multipoint thermometry using 4 fiber-optic sensors (FISO Evolution, FISO) are used to measure the rewarming rates, temperature feedback control is then experimentally implemented, using FPGA-based PID and pulse width modulation (PWM) controller (Lab VIEW, National Instruments) in agreement with known methods, hepatocyte viability (AO/PI, histology, FACS), liver function (bile production, O2 consumption) and injury (ALT, LDH, CD31) are assessed. Convectively warmed livers are used as negative controls. Statistical analysis for correlating predicted damage from ice and cracking vs functional endpoints are also performed.
- PWM pulse width modulation
- the process and system described herein provides an organ rewarming process flow that minimizes or eliminates physical damage to rodent livers from ice crystallization and cracking during rewarming from the cryopreserved vitrified state, with scale-up computational model(s).
- Validation of these findings can be gained with successful transplantation in live rodents, demonstrating a first and meaningful translational step forward for cryopreservation of large tissues and organs.
- An additional intermediate outcome would be extension of this technology to liver sub-systems such as hepatocytes, tissue slices and liver lobes for pharmacological research.
- a longer-term outcome would be success in transplantation of cryopreserved livers and other organs in humans. This would, consequently, allow the practical implementation of organ banking in the cryopreserved state with substantially extended storage times over traditional cold storage. Success in this effort can lead to global changes towards fair organ allocation.
- FIG. 2 is a block diagram illustrating a portion of a process for a feedback-controlled magnetic rewarming system, in accordance with the present disclosure.
- a process for a feedback-controlled magnetic rewarming system 200 includes image analysis, finite element modeling (FEM) simulations and data-driven optimization 202, which provides output information to operation of the radio frequency (RF) coil 204, and to a multi-input, multioutput (MIMO) adaptive controller 206.
- FEM finite element modeling
- MIMO multi-input, multioutput
- a desired rate of warming (dT/dt) 208 is provided via calculation 210, which is the calculated arithmetic difference or error between desired heating rate and current measured heating rate.
- the difference and other similar calculations are generally evaluated digitally using a computer that is connected to a field-programmable gate array (FPGA) controller.
- the desired rate of warming (dT/dt) 208 is provided to the multi -input, multi -output (MIMO) adaptive controller 206 as well.
- the adaptive controller 206 provides its respective inputs to a power supply and matching network 212, which operates the radio frequency (RF) coil 204 to achieve an optimized alternating magnetic field (AMF) amplitude and time-dependent location field free region (FFR) 222.
- RF radio frequency
- AMF optimized alternating magnetic field
- FFR time-dependent location field free region
- a temperature probe placement 218 that monitors the temperature of an organ or biological tissue samples during rewarming to ensure the desired rate of warming (dT/dt) 208 is met.
- This desired rate of warming (dT/dt) 208 is also combined with the image analysis, finite element modeling (FEM) simulations and data-driven optimization 202 to determine an optimized power modulation algorithm 220, which is constrained by dT/dt and spatial difference in temperature (AT), which is also provided to the power supply and matching network 212 via the adaptive controller 206.
- FEM finite element modeling
- AT spatial difference in temperature
- the operation of the adaptive controller 206, interface 210 occur within a Lab VIEW / National Instruments (NI) data acquisition system (Daqs) 216.
- the operation of the radio frequency (RF) coil 204 further provides a temperature probe output 224 which records and transmits temperature measurement data to a FISOTM Evolution temperature (T) readout 214, which can include from multiple (4-8x) sensors in a single temperature probe 224, and these 4-8 analog temperature signals 226 are passed into the interface 210 from the 4 to 8 sensors in the temperature probe output 224 to complete the feedback loop and monitoring of the temperature while a biological tissue sample or organ undergoes the rewarming process of the present disclosure.
- T FISOTM Evolution temperature
- This temperature feedback control system as described herein provides an effective alternating magnetic field to the MNP/CPA composition within an organ to produce the well-controlled heating necessary for ex vivo organ re warming.
- FIG. 3 is a flowchart illustrating a method for preserving and recovering biological tissue, in accordance with the present disclosure.
- a method for preserving and recovering biological tissue 300 is disclosed including a step to perfuse an ex vivo organ with a biological tissue preservation cryoprotectant mixture comprising magnet-responsive particles or magnetic particles 302, followed by a scanning of the ex vivo organ using magnetic particle imaging co-registered with previously acquired radiological images (MRI, CT) 304.
- MRI, CT previously acquired radiological images
- the perfused ex vivo organ is cooled to a first temperature 306, without inducing ice crystallization or cracking.
- This first temperature can range from about 0°C to about -150°C
- the scanning of the ex vivo organ using magnetic particle imaging 304 to generate one or more images representing a distribution of magnet-responsive colloid within the ex vivo organ may be repeated after cooling, in certain examples of the present disclosure.
- the method for preserving and recovering biological tissue 300 may include an additional step of co-registering the magnetic particle imaging with MRI and/or CT imaging of the biological tissue 308, followed by generating 3D computational models for the biological tissue from co-registered images 310, applying a magnetic field to the ex vivo organ using a magnetic field coil that is external to the ex vivo organ 312, and warming the ex vivo organ from the first temperature to a second temperature 314.
- This second temperature target for the rewarming process can range from about 0°C to about 40°C.
- the method for preserving and recovering biological tissue 300 can include where the biological tissue preservation cryoprotectant composition comprises organic solvents including ethylene glycol, sugars, antifreeze proteins, and a magnet-responsive colloid, or a combination thereof.
- portions or steps of the method for preserving and recovering biological tissue 300 can occur in a first geographical location and be performed by a first entity, while other portions or steps of the method for preserving and recovering biological tissue 300 can occur in a first geographical location by a first entity or alternatively in a second geographical location by a second entity. It is envisioned, for example, that process steps associated with removal and cryopreservation of an organ or biological tissue sample can be accomplished in one location by a first entity or organization, while the rewarming and/or transplantation or use of the organ or biological tissue sample can be conducted at a second location by a second entity or organization.
- the method for preserving and recovering biological tissue 300 may include performing one or more finite element modeling-based simulations of coupled electromagnetic and heat transfer in 3D models of the biological tissue using the one or more generated images, and subsequently inputting the optimization results of the one or more simulations including the proportional, integral and derivative gains into a multi-input multioutput (MIMO) adaptive temperature feedback control system to control one or more parameters of the magnetic field.
- MIMO multi-input multioutput
- the one or more parameters of the magnetic field may include frequency, amplitude, power, spatial and temporal localization of the effective alternating magnetic field relative to one or more biological tissue contours, or a combination thereof.
- Certain examples of the method for preserving and recovering biological tissue 300 can include steps to monitor temperature of the ex vivo organ while applying the magnetic field and modulating an amplitude, power or spatiotemporal localization of the alternating magnetic field supplied by the magnetic coil to control a rate of warming of the ex vivo organ.
- the magnetic field coil can supply an alternating magnetic field to the ex vivo organ.
- the method may include perfusing the ex vivo organ with a biological tissue preservation composition including a magnet-responsive colloid prior to scanning using magnetic particle imaging.
- the perfused ex vivo organ may be cooled or warmed at different rates.
- the perfused ex vivo organ can be cooled to the first temperature at a cooling rate from about 0.5°C/min to about 20°C/min or at a rate of warming is greater than 50°C/min.
- Certain examples of the method for preserving and recovering biological tissue 300 include scanning an ex vivo organ using magnetic particle imaging to generate one or more images representing a distribution of a magnet-responsive colloid within the ex vivo organ, applying a magnetic field to the ex vivo organ using a magnetic field coil that is external to the ex vivo organ, and warming the ex vivo organ from a first temperature to a second temperature.
- the steps of performing one or more finite element modeling-based simulations of coupled electromagnetic and heat transfer in 3D models of the biological tissue using the one or more generated images, inputting the optimization results of the one or more simulations including the proportional, integral and derivative gains into a multi -input multioutput (MIMO) adaptive temperature feedback control system to control one or more parameters of the magnetic field may be included where one or more parameters of the magnetic field comprise frequency, amplitude, power, spatial and temporal localization of the alternating magnetic field relative to the biological tissue boundaries or a combination thereof.
- MIMO multi -input multioutput
- Temperature monitoring of the ex vivo organ may be done while applying the magnetic field, and modulating an amplitude, power or spatiotemporal localization of the magnetic field supplied by the magnetic coil to control a rate of warming of the ex vivo organ may be conducted during the method 300, while the magnetic field coil supplies an alternating magnetic field to the ex vivo organ.
- all of the steps of perfusing an ex vivo organ with a biological tissue preservation composition comprising a magnet-responsive colloid, scanning the ex vivo organ using magnetic particle imaging; cooling the perfused ex vivo organ to a first temperature, scanning an ex vivo organ using magnetic particle imaging to generate one or more images representing a distribution of magnet-responsive colloid within the ex vivo organ, co-registering the magnetic particle imaging with MRI and/or CT imaging of the biological tissue generating 3D computational models for the biological tissue from co-registered images, applying a magnetic field to the ex vivo organ using a magnetic field coil that is external to the ex vivo organ, and warming the ex vivo organ from the first temperature to a second temperature occur in a single location and are conducted by a single entity or organization.
- the method may further include performing one or more finite element modelingbased simulations of coupled electromagnetic and heat transfer in 3D models of the biological tissue using the one or more generated images, inputting the optimization results of the one or more simulations including the proportional, integral and derivative gains into a multi-input multi-output (MIMO) adaptive temperature feedback control system to control one or more parameters of the magnetic field, monitoring temperature of the ex vivo organ while applying the magnetic field; and modulating an amplitude, power or spatiotemporal localization of the magnetic field supplied by the magnetic coil to control a rate of warming of the ex vivo organ, cooling the perfused ex vivo organ to a first temperature prior to scanning the ex vivo organ using magnetic particle imaging, cooling the perfused ex vivo organ to a first temperature after scanning the ex vivo organ using magnetic particle imaging, or any combination of steps as described herein in modified order of steps.
- MIMO multi-input multi-output
- one or more of the acts depicted herein may be carried out in one or more separate acts and/or phases.
- the terms “including,” “includes,” “having,” “has,” “with,” or variants thereof are used in either the detailed description and the claims, such terms are intended to be inclusive in a manner similar to the term “comprising.”
- the term “at least one of’ is used to mean one or more of the listed items may be selected.
- the term “on” used with respect to two materials, one “on” the other means at least some contact between the materials, while “over” means the materials are in proximity, but possibly with one or more additional intervening materials such that contact is possible but not required.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Heart & Thoracic Surgery (AREA)
- Environmental Sciences (AREA)
- Wood Science & Technology (AREA)
- Radiology & Medical Imaging (AREA)
- Dentistry (AREA)
- Biophysics (AREA)
- Pathology (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Medical Informatics (AREA)
- Molecular Biology (AREA)
- Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
Un système et un procédé de conservation et de récupération de tissu biologique sont divulgués. Le système et le procédé consistent à perfuser un organe ex vivo avec une composition de conservation de tissu biologique contenant un colloïde réagissant au magnétisme, analyser l'organe ex vivo à l'aide d'une imagerie par particules magnétiques, et refroidir l'organe ex vivo perfusé à une première température. Le procédé consiste également à analyser un organe ex vivo à l'aide d'une imagerie par particules magnétiques pour générer une ou plusieurs images représentant une distribution de colloïde réagissant au magnétisme à l'intérieur de l'organe ex vivo. Le procédé consiste également à co-enregistrer l'imagerie par particules magnétiques avec une imagerie IRM et/ou CT du tissu biologique, générer des modèles informatiques 3D pour le tissu biologique à partir d'images co-enregistrées, appliquer un champ magnétique alternatif efficace indiqué par une commande par retour d'informations de température sur l'organe ex vivo à l'aide d'une bobine de champ magnétique qui est externe à l'organe ex vivo, et chauffer l'organe ex vivo de la première température à une seconde température.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US202263383559P | 2022-11-14 | 2022-11-14 | |
US63/383,559 | 2022-11-14 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2024107310A1 true WO2024107310A1 (fr) | 2024-05-23 |
Family
ID=91085202
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2023/035675 WO2024107310A1 (fr) | 2022-11-14 | 2023-10-23 | Commande par retour d'informations de température guidée par image pour réchauffement magnétique sans dommage et récupération de tissu cryoconservé |
Country Status (1)
Country | Link |
---|---|
WO (1) | WO2024107310A1 (fr) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20100233670A1 (en) * | 2006-02-13 | 2010-09-16 | Zohar Gavish | Frozen Viable Solid Organs and Method for Freezing Same |
US20150264918A1 (en) * | 1997-09-23 | 2015-09-24 | The Department Of Veteran Affairs | Compositions, methods and devices for maintaining an organ |
US20220132835A1 (en) * | 2013-03-15 | 2022-05-05 | Regents Of The University Of Minnesota | Cryopreservative compositions and methods |
-
2023
- 2023-10-23 WO PCT/US2023/035675 patent/WO2024107310A1/fr unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20150264918A1 (en) * | 1997-09-23 | 2015-09-24 | The Department Of Veteran Affairs | Compositions, methods and devices for maintaining an organ |
US20100233670A1 (en) * | 2006-02-13 | 2010-09-16 | Zohar Gavish | Frozen Viable Solid Organs and Method for Freezing Same |
US20220132835A1 (en) * | 2013-03-15 | 2022-05-05 | Regents Of The University Of Minnesota | Cryopreservative compositions and methods |
Non-Patent Citations (2)
Title |
---|
CHIU-LAM ANDREINA, STAPLES EDWARD; PEPINE CARL J; RINALDI CARLOS; CRAYTON PRUITT J; : "Perfusion, cryopreservation, and nanowarming of whole hearts using colloidally stable magnetic cryopreservation agent solutions", SCIENCE ADVANCES, AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE, US, vol. 7, no. 2, 8 January 2021 (2021-01-08), US , XP093174693, ISSN: 2375-2548, DOI: 10.1126/sciadv.abe3005 * |
TAY ZHI WEI, CHANDRASEKHARAN PRASHANT; CHIU-LAM ANDREINA; HENSLEY DANIEL W.; DHAVALIKAR ROHAN; ZHOU XINYI Y.; YU ELAINE Y.; GOODWI: "Magnetic Particle Imaging-Guided Heating in Vivo Using Gradient Fields for Arbitrary Localization of Magnetic Hyperthermia Therapy", ACS NANO, AMERICAN CHEMICAL SOCIETY, US, vol. 12, no. 4, 24 April 2018 (2018-04-24), US , pages 3699 - 3713, XP093174699, ISSN: 1936-0851, DOI: 10.1021/acsnano.8b00893 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Manuchehrabadi et al. | Improved tissue cryopreservation using inductive heating of magnetic nanoparticles | |
Cline et al. | MR-guided focused ultrasound surgery | |
Pauly et al. | Magnetic resonance-guided high-intensity ultrasound ablation of the prostate | |
Auboiroux et al. | Ultrasonography-based 2D motion-compensated HIFU sonication integrated with reference-free MR temperature monitoring: a feasibility study ex vivo | |
EP2519324B1 (fr) | Appareil thérapeutique | |
US20120071746A1 (en) | Magnetic resonance thermometry using prf spectroscopy | |
Rieke et al. | Comparison of temperature processing methods for monitoring focused ultrasound ablation in the brain | |
Eggen et al. | Ex vivo diffusion tensor MRI of human hearts: relative effects of specimen decomposition | |
Hoogenboom et al. | In vivo MR guided boiling histotripsy in a mouse tumor model evaluated by MRI and histopathology | |
EP2528493A1 (fr) | Procédé et appareil destinés à estimer la température dans un corps | |
JP2005046588A (ja) | 磁気共鳴断層画像法による自己参照型・体動追従型の非侵襲体内温度分布計測方法及びその装置 | |
Kangasniemi et al. | Multiplanar MR temperature‐sensitive imaging of cerebral thermal treatment using interstitial ultrasound applicators in a canine model | |
Kowalski et al. | Optimization of electromagnetic phased-arrays for hyperthermia via magnetic resonance temperature estimation | |
MacDonell et al. | Robotic assisted MRI-guided interventional interstitial MR-guided focused ultrasound ablation in a swine model | |
Schwenke et al. | An integrated model-based software for FUS in moving abdominal organs | |
Fuentes et al. | High-fidelity computer models for prospective treatment planning of radiofrequency ablation with in vitro experimental correlation | |
Huang et al. | MR-guided focused ultrasound for brain ablation and blood–brain barrier disruption | |
Benson et al. | Mathematical model formulation and validation of water and solute transport in whole hamster pancreatic islets | |
WO2024107310A1 (fr) | Commande par retour d'informations de température guidée par image pour réchauffement magnétique sans dommage et récupération de tissu cryoconservé | |
Sommer et al. | Applicators for magnetic resonance–guided ultrasonic ablation of benign prostatic hyperplasia | |
Turner et al. | Measuring temperature using MRI: a powerful and versatile technique | |
WO2018112472A1 (fr) | Système, procédé et support accessible par ordinateur permettant de déterminer un profil de température d'imagerie par résonance magnétique | |
Berman et al. | MRI of transplanted neural stem cells | |
Samset | Temperature mapping of thermal ablation using MRI | |
Petrusca et al. | A nonparametric temperature controller with nonlinear negative reaction for multi-point rapid MR-guided HIFU ablation |