WO2007059069A2 - Imagerie fonctionnelle pour sujets mobiles - Google Patents

Imagerie fonctionnelle pour sujets mobiles Download PDF

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Publication number
WO2007059069A2
WO2007059069A2 PCT/US2006/044065 US2006044065W WO2007059069A2 WO 2007059069 A2 WO2007059069 A2 WO 2007059069A2 US 2006044065 W US2006044065 W US 2006044065W WO 2007059069 A2 WO2007059069 A2 WO 2007059069A2
Authority
WO
WIPO (PCT)
Prior art keywords
subject
brain
cables
fiber
optical
Prior art date
Application number
PCT/US2006/044065
Other languages
English (en)
Other versions
WO2007059069A3 (fr
Inventor
Randall L. Barbour
Robert L. Muller
Original Assignee
Barbour Randall L
Muller Robert L
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Barbour Randall L, Muller Robert L filed Critical Barbour Randall L
Publication of WO2007059069A2 publication Critical patent/WO2007059069A2/fr
Publication of WO2007059069A3 publication Critical patent/WO2007059069A3/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/316—Modalities, i.e. specific diagnostic methods
    • A61B5/369—Electroencephalography [EEG]
    • A61B5/384—Recording apparatus or displays specially adapted therefor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0073—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by tomography, i.e. reconstruction of 3D images from 2D projections
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0033—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room
    • A61B5/004—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room adapted for image acquisition of a particular organ or body part
    • A61B5/0042—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room adapted for image acquisition of a particular organ or body part for the brain
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/316—Modalities, i.e. specific diagnostic methods
    • A61B5/369—Electroencephalography [EEG]

Definitions

  • the present invention relates to imaging brain activity in a subject, and more specifically, relates to imaging brain activity in a freely moving animal or freely moving human.
  • Noninvasive imaging technologies used to explore such coupling include magnetic resonance (MR), positron emission tomography (PET), single photon emission computerized tomography (SPECT) and magnetic encephalography (MEG), each of which requires large-scale instruments whose sensing array is too large to be mobile. Therefore, use of these methods requires the subject be immobile. Additionally, even small movements inside the sensing environment (e.g. in the MR magnet) can severely degrade image quality.
  • MR magnetic resonance
  • PET positron emission tomography
  • SPECT single photon emission computerized tomography
  • MEG magnetic encephalography
  • Electroencephalography is a method that has been used to explore brain function in mobile subjects, including laboratory animals.
  • EEG is a neurological technique that involves attaching electrodes to a person's or animal's head to record electrical brain activity over time. This method has the disadvantage of poor spatial resolution when implemented with scalp electrodes and is not greatly improved with electrodes inserted into the brains of animals. In addition, it is sensitive only to electrical activity, leaving untapped the potential impact that variations in hemodynamic states can have for understanding brain function and behavior.
  • Hemodynamics is the aspect of cardiovascular physiology that deals with the regulation of blood flow throughout the body, including the brain).
  • a potential means of measuring brain hemodynamic brain responses in freely moving animals involves optical methods.
  • One approach is to mount a charge-coupled device (CCD) camera onto the skull of an animal.
  • CCD charge-coupled device
  • a fiber optic bundle inserted through the skull and into the brain connects to the CCD device and enables optical measurements on freely moving animals with or without concurrent EEG recordings.
  • camera-based techniques have the disadvantage of restricting measurements to only one or a few brain parts at a time.
  • Diffuse optical tomography is capable of recording hemodynamic signals in deep tissues of the head and other body parts.
  • Diffuse optical imaging (DOI) or diffuse optical tomography (DOT) is a medical imaging modality which currently uses near-infrared light to detect changes in hemodynamic variables such as oxyhemoglobin, deoxyhemoglobin and quantities derived from these primary variables in conjunction with tomographic computations to generate images of body parts.
  • DOI Diffuse optical imaging
  • DOT diffuse optical tomography
  • DOT diffuse optical tomography
  • DOT in intact, freely moving animals would be of great value in the development and testing of new drugs and for a range of clinical diagnoses and related assessments.
  • a system for monitoring brain activity in a freely moving animal or human subject, which comprises a first device adapted for attaching fiber optical cables to the head of a subject.
  • a second device is detachably coupled to the first device and holds the fiber optical cables.
  • the fiber optic cables provide a communicating light path between a tomographic imaging device and the brain of the subject when the second device is plugged into (or coupled to) the first device, in one embodiment, in a manner equivalent to plugging a male connector into a female connector.
  • a commutator is interposed between the tomographic imaging device and the fiber optic cable wherein the commutator allows the subject to be mobile within a defined area.
  • the commutator may provide mobility two dimensional linear mobility, rotational mobility or both linear and rotational mobility.
  • the tomographic imaging device is attached to and moves with the commutator, allowing the subject two dimensional linear mobility, rotational mobility or both.
  • the first device is adapted to be removably attached to the head of the subject.
  • the first and second devices hold a drug delivery member for delivering drugs into the brain of the subject.
  • the optical fibers are attached to the brain using surgical implantation.
  • the imaging device includes a computer.
  • the commutator includes a computer for tracking the subject's head position.
  • the optical fibers held by the first device are recessed within the first device.
  • the second device includes an LED
  • the system further includes a video camera for recording the LED and the subject's location in a specified area, and the subject's location is displayed and recorded by a recording device.
  • the optical fiber of the optical fiber cables is implanted in the brain of the subject.
  • an electrical cable is passed through the first and second devices and coinmunicates with the brain of the subject to provide brain images.
  • EEG readings are obtained from the brain using the electrical cable.
  • DOT readings are obtained from the brain using the optical fiber cables.
  • a method of monitoring brain activity in a mobile animal or human comprises communicating with the head of a subject using fiber optical cables. Free motion of the subject is provided within a defined area. A light path is provided using the fiber optical cables between a tomographic imaging device and the brain of the subject, and the brain of the subject is imaged using the tomographic imaging device.
  • FIG. 1 is a photograph of a cap assembly according to the present invention depicting a first cap and a second cap;
  • FIG. 2 is a perspective view of the assembled cap assembly shown in Fig. 1 ;
  • FIG. 3 is a schematic of a functional imaging system according to an embodiment of the invention.
  • FIG. 4 is a photograph of an animal subject having the cap assembly shown in Figs. 1 and 2 attached to it's skull.
  • the development of diffuse optical tomography (DOT) has made it possible to record hemodynamic signals in deep tissues of the head and other body parts.
  • the present invention can utilize DOT, EEG and fiber optic techniques to generate images and assess blood supply and electrical activity in the brain of a mobile subject.
  • DOT diffuse optical tomography
  • small animals such as rats
  • the adaptation of the DOT technique to mobile animals and humans provides new capabilities for investigating complex behaviors and executive functions.
  • the present invention envisions combining DOT with other sensing technologies including electroencephalography (EEG) and single cell recording.
  • the present invention enables the assessment of real time effects on the brain during normal behavior, after selected stimulation, or during drug infusion into a mobile subject.
  • an illustrative embodiment of a two-part cap assembly 10 for use with a functional imaging recording system 100 (shown in Fig. 3) includes a first cap 14 and a second cap 18.
  • the cap assembly 10 is adapted for a DOT plus EEG animal implant.
  • the first cap 14 maybe attached to the head/scalp of a subject using suitable adhesive, or a detachable support structure.
  • the first cap 14 may additionally be secured on the scalp by fiber optical cable that passes through the first cap 14 and are surgically implanted into the brain of the subject.
  • the second cap 18 detachably mates with the first cap 14.
  • the second cap 18 includes tubes 52 having openings or apertures therethrough 52a, and electrical connectors 56.
  • the first cap 14 includes apertures 86, shown on a bottom surface 84, and passing therethrough to a top surface 82 (not shown). Both the tubes 52 and electrical connectors 56 have complimentary receiving (female) openings, apertures 86 and electrical connectors (not shown) in the top surface 82 of the first cap 14, so that the first and second caps 14, 18 mate and are flush when assembled as shown in Fig. 2. Thus, when assembled, fiber optic bundles 124 (shown in Figs. 3 and 4) can pass through the mating apertures 52a and 86 for attachment to the subject brain or scalp.
  • the second cap 18 also serves to anchor an umbilical of optical fiber cables together with other optional sensing and/or drug delivery tethers or tubes (e.g., EEG leads, microdialysis lines, etc.).
  • An exemplary access aperture 22 is shown in Fig. 2 for administering drugs directly to the brain of a subject.
  • the access aperture exits the second cap 18 at hole 22a and exits the first cap 14 at hole 22b.
  • the cap assembly may also be a helmet-like assembly adapted for the human head and could be affixed to the head using a chin strap.
  • the cap assembly 10 is adapted to be used on a subject rat 110 (shown in Figs. 3 and 4).
  • the first cap 14 is adapted to attach to the head of the subject rat 110 where a bottom surface 84 is adapted to substantially mate with the skull of the rat 110 (shown in Figs. 3 and 4).
  • the first cap 14 is adapted to support sixteen 1.8 mm optical fibers in a distributed array integrated with EEG leads that are inserted through drilled skull holes into the brain of the animal subject 110.
  • subject animal 110 has fiber bundles 124 attached to its skull.
  • An electrical cable 142 connects the EEG leads implanted in the brain of the subject 110 to recording equipment 152 at the other end of the cable (shown in Fig. 3).
  • the numerous fiber optic bundles 124 can be gathered together as an optical tether 125 shown in Fig. 3. If numerous electrical cables are also used, an electrical tether 129 shown in Fig. 3 can also be used.
  • the optical fiber cables 124 (shown in Fig. 4, and as a bundled optical fiber cable tether 125 in Fig. 3) pass through the first and second caps 14, 18 helping to attach the two together. In this way, the first cap 14 can be permanently attached and sealed to the skull of an animal subject (shown in Fig. 4) limiting exposure of the skull to infection.
  • the fibers are also recessed within the first cap 14 to reduce possible optical cross-talk.
  • Mounted on the second cap 18 is an LED 132 (shown in Figs. 3 and 4) to facilitate precise video tracking of the subject animal's 110 locomotion.
  • the video camera 172 and screen 176 easily distinguish the LED light source and thus record the animals position within the arena 148.
  • the first cap 14 and the second cap 18 are held together by the tight tolerances of the electrical 128 and optical 124 leads (shown in Fig. 4, and shown as bundles optical and electrical tethers 125, 129, respectively in Fig. 3) and by external clips 62 (shown in Fig. 1).
  • exemplary portals or apertures 22a, 22b allow drug delivery via, for example, a microdialysis probe.
  • the illustrated cap assembly can be adapted in many ways to increase or alter the optical array density and the position and number of additional sensing elements. It is understood that similar devices can be designed to capture a variety of other optical or optical dependent signals such as fluorescence, opto-acoustic and photoacoustic information.
  • an overhead, motor-driven commutator 142 eliminates the problem of entanglement of the electrical 128 and optical 124 tethers as the animal walks around.
  • the commutator 142 is capable of turning to compensate for turns of the subject rat 110.
  • Control of the commutator 142 is implemented with a computer/tracker 146 that senses head direction.
  • the commutator 142 would be attached to an overhead two-axis motor driven translator (not shown) that will reposition the entire assembly to follow the subject's movement.
  • an assembled cap 98 includes first and second caps 14, 18.
  • the bottom surface 84 of the first cap 14 includes apertures 86 for allowing fiber optic bundles to pass therethrough.
  • Anchoring tabs 92 assist in connecting the bottom surface 84 of the first cap 14 to the skull of the subject by using adhesive over and/or around the edges of the tabs 92 to attach the tabs to the scalp and thereby attach the first cap 14 to the skull of the subject.
  • the first cap 14 can further be attached to the skull by sealing the edge of the first cap to the skull with adhesive, or when the first cap is intended to be more easily removable, using a removable adhesive strip over the tabs 92 to attach the first cap 14 to the scalp of the subject. Further, a chin strap or other suitable means for human subjects can be used where the first cap is intended to be easily removable.
  • the imaging system 100 for recording the blood flow and electrical stimulation in the subject's brain includes an animal subject 110, in this case a rat, having the cap apparatus 10 including the first cap 14 and the second cap 18 attached to its head.
  • An optical tether 125 including multiple optical bundles or optical fiber cables 124 (as can be seen in Fig. 4) and an electrical tether 129 which can include one or multiple electrical cables 128 (also shown in Fig. 4) extend upward from the cap apparatus 10 to a compact Dynamic Near Optical Tomography (DYNOT) system/imaging device 142.
  • DYNOT Dynamic Near Optical Tomography
  • the compact system 142 may include a commutator wherein the compact system turns with the optical tether and the electrical tether in concert with the subject 110 so that the subject can move freely in the arena 148 within the environmental chamber 116.
  • the electrical tether 129 is further connected to an electro- physiology recording system 152 for recording the electrical activity in the brain of the subject 110.
  • the DYNOT compact system 142 and the electro-physiology recording system 152 are synchronized.
  • the video camera is in the environmental chamber 116 to record the position of the tracking LED 132.
  • the video camera 172 is connected to the video screen 176 which in turn is connected to a computer 184 with the capability for frame-by-frame recording and analysis of the video.
  • the light from the LED 132 is also monitored on the video screen 176 so that the subject' s position visible in real time.
  • the cap assembly 10 is attached to a subject animal/rat 110.
  • the adhesive 192 surrounds and affixes the cap assembly 10 to the skull of the rat 110.
  • the LED 132 is adjacent the optical fiber bundles 124 and an electrical cable 128 is also shown.
  • the optical fiber bundles and the electrical cable are tethered together and attached to the DYNOT system 142 (shown in Fig. 3) directly above the subject 110.
  • the subject rat 110 is freely mobile within the arena 148.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Veterinary Medicine (AREA)
  • Biophysics (AREA)
  • Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Public Health (AREA)
  • Physics & Mathematics (AREA)
  • Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Psychiatry (AREA)
  • Psychology (AREA)
  • Neurology (AREA)
  • Measurement Of The Respiration, Hearing Ability, Form, And Blood Characteristics Of Living Organisms (AREA)

Abstract

L'invention se rapporte à un système pour surveiller l'activité cérébrale d'un animal ou d'un être humain en mouvement. Ce système comprend un premier dispositif servant à fixer des câbles à fibre optique sur la tête d'un sujet. Un deuxième dispositif est accouplé de manière libérable avec ledit premier dispositif et maintient les câbles à fibre optique. Lesdits câbles à fibre optique établissent un chemin lumineux de communication entre un dispositif d'imagerie par tomographie et le cerveau du sujet, lorsque le deuxième dispositif est introduit dans le premier dispositif à la manière d'un connecteur mâle enfiché dans un connecteur femelle.
PCT/US2006/044065 2005-11-11 2006-11-13 Imagerie fonctionnelle pour sujets mobiles WO2007059069A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US73578705P 2005-11-11 2005-11-11
US60/735,787 2005-11-11

Publications (2)

Publication Number Publication Date
WO2007059069A2 true WO2007059069A2 (fr) 2007-05-24
WO2007059069A3 WO2007059069A3 (fr) 2007-12-21

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011132756A1 (fr) 2010-04-21 2011-10-27 国立大学法人東北大学 Unité d'électrodes pour encéphalogramme destinée à des petits animaux et son emploi dans un système de mesure
CN103932702A (zh) * 2014-04-24 2014-07-23 上海谱康电子科技有限公司 脑电采集传送系统和方法
CN110477871A (zh) * 2019-09-10 2019-11-22 南方科技大学 用于自由移动状态下实验动物脑成像的光声层析成像装置
WO2022218723A1 (fr) * 2021-04-14 2022-10-20 Centre National De La Recherche Scientifique Dispositif et procédé d'imagerie de cibles mobiles

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6475188B1 (en) * 1999-05-20 2002-11-05 Anthony David Baxter Bilateral microinjector pump for freely moving animals in an operant chamber
US6602220B1 (en) * 2000-05-26 2003-08-05 The Research Foundation Of State University Of New York Miniature air-controlled drug selector and delivery device portable by small animals
WO2005038491A2 (fr) * 2003-10-17 2005-04-28 Hammersmith Imanet Limited Procede et logiciel d'execution de correction de mouvement pour un scanneur tomographique
US20050107716A1 (en) * 2003-11-14 2005-05-19 Media Lab Europe Methods and apparatus for positioning and retrieving information from a plurality of brain activity sensors
US20050203366A1 (en) * 2004-03-12 2005-09-15 Donoghue John P. Neurological event monitoring and therapy systems and related methods

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6475188B1 (en) * 1999-05-20 2002-11-05 Anthony David Baxter Bilateral microinjector pump for freely moving animals in an operant chamber
US6602220B1 (en) * 2000-05-26 2003-08-05 The Research Foundation Of State University Of New York Miniature air-controlled drug selector and delivery device portable by small animals
WO2005038491A2 (fr) * 2003-10-17 2005-04-28 Hammersmith Imanet Limited Procede et logiciel d'execution de correction de mouvement pour un scanneur tomographique
US20050107716A1 (en) * 2003-11-14 2005-05-19 Media Lab Europe Methods and apparatus for positioning and retrieving information from a plurality of brain activity sensors
US20050203366A1 (en) * 2004-03-12 2005-09-15 Donoghue John P. Neurological event monitoring and therapy systems and related methods

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011132756A1 (fr) 2010-04-21 2011-10-27 国立大学法人東北大学 Unité d'électrodes pour encéphalogramme destinée à des petits animaux et son emploi dans un système de mesure
US9078584B2 (en) 2010-04-21 2015-07-14 Tohoku University Electroencephalogram electrode unit for small animals and measurement system using the same
CN103932702A (zh) * 2014-04-24 2014-07-23 上海谱康电子科技有限公司 脑电采集传送系统和方法
CN110477871A (zh) * 2019-09-10 2019-11-22 南方科技大学 用于自由移动状态下实验动物脑成像的光声层析成像装置
WO2022218723A1 (fr) * 2021-04-14 2022-10-20 Centre National De La Recherche Scientifique Dispositif et procédé d'imagerie de cibles mobiles
FR3121999A1 (fr) * 2021-04-14 2022-10-21 Centre National De La Recherche Scientifique Dispositif et procédé d’imagerie de cibles mobiles

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