The present disclosure relates generally to functional magnetic resonance (fMRI) systems and more particularly to a system and platform for awake fMRI of an animal subject.
Preclinical fMRI has provided a unique functional mapping scheme for basic mechanistic and translational studies. In particular, animal fMRI enables brain-wide hemodynamic measurements, showing the non-invasive and longitudinal imaging capability, which is crucial for diagnostic and therapeutic testing in animal models. More importantly, preclinical fMRI can be combined with other imaging modalities, e.g., electrophysiological recordings or fiber photometry, to measure the brain dynamic signals across the neuro-glial-vascular (NGV) network. This multi-modal neuroimaging scheme can provide critical cross-scale information to identify bio-marker or therapeutic targets of a broad spectrum of brain disorders and lesions. An ongoing challenge of preclinical fMRI is how to reliably implement it in animal models with high throughput. Additional challenges of brain imaging of animal models or subjects include the susceptibility-related inhomogeneity (e.g., air-tissue interface distortion) that can affect image quality, signal sensitivity (e.g., achievement of cellular or micro-vascular specificity needs higher SNR for microscopic imaging), and limited space for a multi-modal environment setup.
In accordance with an embodiment, a system for awake functional magnetic resonance imaging (fMRI) of an animal subject includes an RF coil apparatus and a tunnel apparatus. The RF coil apparatus includes an RF coil configured to be implanted on the animal subject, a head post coupled to the RF coil and comprising a housing and a circuit board positioned within the housing, and a connector coupled to the circuit board. The tunnel apparatus includes a first end having an opening, a second end, a slot positioned on a top side of the tunnel apparatus and configured to movably receive the head post of the RF coil apparatus, and an inner region configured to receive the animal subject and allow the animal subject to move from the first end to the second end.
The present disclosure will hereafter be described with reference to the accompanying drawings, wherein like reference numerals denote like elements.
The present disclosure describes a system and apparatus for awake functional magnetic resonance imaging (fMRI) of an animal subject or animal model (e.g., a rodent, passerine, or small primate). In some embodiments, the system can include an implantable RF coil apparatus and a tunnel apparatus. The system may be configured to be used with a magnetic resonance imaging (MM) system (e.g., known MRI systems for imaging of animal subjects including preclinical MRI systems).to acquire magnetic resonance (MR) signals or data from the animal subject, for example, using pulse sequences for fMRI. In some embodiments, the acquired MR data may be used to generate fMRI images or maps. The RF coil apparatus may be used to receive radio frequency (RF) signals, to transmit RF signals, or to both receive and transmit RF signals. The tunnel apparatus may be configured to provide an awake animal head-fixation device for the animal subject and to allow the animal subject to run through the tunnel apparatus with a head-fixed posture and to fix the head position of the animal subject for imaging, for example, brain imaging.
In some embodiments, the RF coil apparatus includes an implantable RF coil and a circuit board coupled to the implantable RF coil. The implantable RF coil may be mounted directly on the skull (and brain) (or inserted into the craniotomy, i.e., a large opening) of the animal subject. The circuit board (e.g., a printed circuit board (PCB)) may have a cover or housing and can be used as a head post when positioned in the tunnel apparatus and can be used to restrain the animal subject in a head-fixed position. In some embodiments, the circuit board can include an RLC circuit which can be adjusted for various applications. In some embodiments, the RF coil apparatus can also include a connector coupled to the circuit board. The tunnel apparatus can include a slot or track that may be configured to receive the circuit board (or head post) of the RF coil apparatus to allow an animal subject with the implanted RF coil apparatus to move voluntarily (or passively) through the tunnel apparatus with a head-fixed posture. In some embodiments, the tunnel apparatus allows the animal subject to move through the tunnel apparatus to an area where the head post can be fixed to the slot or track (e.g., a head fixation point). In some embodiment, when the tunnel apparatus is positioned in a bore of a MM system, the head fixation point may correspond to a geometric center of the MRI system for imaging. In some embodiments, the tunnel apparatus may include an attachment or connection mechanism which may be used to removable attach a cassette (e.g., a miniaturized cassette) that may be configured to include a preamplifier and, in some embodiments, a transmit/receive switch. The cassette may be connected to the connector of the RF coil apparatus.
The disclosed system for awake functional magnetic resonance imaging (fMRI) of an animal subject advantageously can improve image quality, provide a superior signal-to-noise ratio (SNR) measurement, and improve ease of use for acquiring images (e.g., brain images) of an animal subject. To address the physiological confound, the system can advantageously be implemented for imaging without anesthetic treatment for the animal subject. Because the RF coil of the apparatus is mounted directly on the skull of the animal subject, there is less motion-induced loading change, which significantly reduces the B1 variability. In some embodiments, no additional tuning or matching is needed once an adjustable capacitor (e.g., a trimmer) of the circuit board of the RF coil apparatus is set with appropriate values for an application. The geometry and mounting scheme of the RF coil apparatus advantageously reduces air-tissue B0 and motion-related loading-based B1 artifacts. The tunnel apparatus which can include a slot to movably (or slidably) receive the head post (i.e., the circuit board and housing) of the RF coil apparatus allows an animal subject to move through an inner chamber of the runnel apparatus and can advantageously reduce the stress of the animal subject(s) and enable behavioral testing of the animal subject(s). The miniaturized removable (e.g., plug-and-play) cassette (e.g., holding a preamplifier and TR switch) can improve the SNR of images generated using the MR data acquired with the RF coil apparatus. In some embodiments, the design and loading characteristics of the RF coil apparatus can be designed specifically for a designed application. For example, the RF coil apparatus may be designed for specific species application (e.g., rodent, passerine, and small primate). In some embodiments, the disclosed system for awake functional magnetic resonance imaging (fMRI) of an animal subject can allow multi-modal schemes, for example, the system can be combined with a miniaturized camera (or cameras), glass/coverslip plug implantation for optical imaging, fiber photometry, or electrophysiological recordings.
As mentioned above, in some embodiments, the system for awake fMRI of an animal subject (or animal model) can include an RF coil apparatus and a tunnel apparatus.
In some embodiments, the RF coil 104 may advantageously be directly mounted to the skull (and brain) of the animal subject 102. Accordingly, the RF coil 104 may be implanted on the head of the animal subject 102. In some embodiments, the implanted RF coil can be fixed using a material such as, for example, dental cement. Minimizing the distance of the RF coil to the skull can produce an idealized loading scheme and improve B1 sensitivity. In some embodiments, the RF coil 104 may be formed from, for example, magnet wire (e.g., copper wire coated with a thin layer of enameled insulation. In some embodiments, the RF coil 104 may be formed using standard copper wire or be printed on a PCB as copper layers. In some embodiments, the RF coil 104 may be formed from a flexible circuit mounted to a rigid material (e.g., dense rubber or other nonconductive polymer) to ensure proper mounting for head fixation. The size and loading characteristics of the RF coil 104 may be designed specifically for the imaging application desired by an operator or end user. This can allow for designs of the RF coil 104 to be built for specific species applications such as, for example, rodent, passerine, and small primate. The overall weight of the RF coil apparatus 100 may be dependent on the size and shape of the RF coil 104. In some embodiments, the overall weight of the RF coil apparatus 100 may be in the range of 2.0 g to 2.5 g which can allow for implantation in smaller animal subjects (e.g., mice). In some embodiments, the size of the RF coil 104 may be in the range of 0.5 mm to mm, which can allow for coverage of the whole brain of the animal subject 102, as well as, for example, direct implantation above the dura on the skull through craniotomy. Animal subjects with RF coil implantations can have a high durability and attachment longevity, which can be maintained, for example, for over six weeks.
In some embodiments, various coil or loop shapes can be used for RF coil 104 to provide, for example, a single channel transceiver. For example, in some embodiments, the RF coil 104 may be implemented as a single loop coil 202 as shown in
Returning to
The connector 108 of the RF coil apparatus 100 is coupled to the circuit board 106 and housing 110. In some embodiments, the connector may be, for example, a micro coaxial (MCX) connector, a subMiniature version A (SMA) connector, or a subMiniature version B (SMB) connector. In some embodiments, the connector 108 can be further customized to minimize or eliminate the need for plug adapters which can cause disruptions resulting in poor signal transmission.
The first end 804 of the tunnel apparatus 800 can include an opening or entrance 806 (also shown in
In some embodiments, the size and shape of the tunnel apparatus 800 can be configured based on the size of a bore (i.e., as defined by the gradient size) of an MM system in which the tunnel apparatus 800 may be positioned for imaging of the animal subject. In some embodiments, the tunnel apparatus 800 may be configured for use with gradient bore sizes ranging from 6 cm to 21 cm.
As mentioned, an animal subject may move through the inner region (or chamber) 810 of the tunnel apparatus 800 from the first end 804 to the second end 808.
The second end 808 of the tunnel apparatus 800 may be configured to allow the circuit board/head post 846 of the RF coil apparatus 840 on the animal subject 842 to be fixed to the slot (or track) 814.
As mentioned, the circuit board 846 of the RF coil apparatus 800 can be used as a head post to restrain the animal subject in a head-fixed position.
In some embodiments, a cassette 860 (e.g., a miniaturized cassette) may be used to house a preamplifier and transmit/receive (T/R) switch that can be attached to the tunnel apparatus 800 and connected to the circuit board/head post 846 (and the RF coil, not shown) via the connector 848. As mentioned above, the connector 848 of the RF coil apparatus can be customized for different needs and applications. The RF coil apparatus 840 can be connected to an MM system via the preamplifier in the cassette 860 (e.g., using an RF cable 864) to ensure efficient and significantly improved SNR. The cassette 860 can be configured to be attached to the tunnel apparatus 800, for example, the cassette 860 may be attached to the tunnel apparatus 800 using one or more attachment or connection mechanisms 824 on the top side 802 of the tunnel apparatus 800. In some embodiments, the cassette 860 (e.g., a preamplifier with an integrated T/R switch) may be directly connected (or plugged into) the RF coil apparatus circuit board/head post 846 using the connector 848 and, for example, a cable 862 of the cassette 860. In some embodiments, when attached to the tunnel apparatus 800 and connected to the connector 848 of the circuit board/head post 846 of the implanted RF coil apparatus, the cassette 860 can also serve to fix the circuit board/head post 846 to the tunnel apparatus 800 to eliminate the longitudinal motion of the animal subject (not shown). In some embodiments, a separate transmit coil (e.g., a double-ring (Helmholtz-style) transmit coil) may be positioned laterally across the animal subject's head on the top side 802 of the tunnel apparatus 800. The implanted RF coil (not shown) can then act as a receive only coil which can eliminate the need to include a T/R switch in the preamplifier circuit block of the cassette 860.
In some embodiments, the system for awake fMRI of an animal subject can be incorporated with multi-modal brain imaging sets, such as, for example, miniaturized microscopy, fiber bundle imaging, and single/multichannel fiber photometry, which can simultaneously detect cell-type specific dynamics from neurons and astrocytes. In some embodiments, to provide multi-model schemes, the system for awake fMRI of an animal subject can be customized to include additional elements such as, for example, a miniaturized camera set (e.g., including an GRINS lens or multi-bundle fibers), as well as optogenetic stimulation fibers, electrodes, and microinjection capillaries. In some embodiments, the system for awake fMRI of an animal subject used in a multi-modal application, can allow longitudinal recording of cross-scale brain dynamic signals by expressing genetically encoded indicators for Calcium, Glutamate, or neuromodulators, and voltage sensors.
In some embodiments, awake fMRI may be used to study the cross-scale brain function across a large pool of transgenic mouse lines. In some embodiments, fMRI images generated from MR data (or signals) acquired using the disclosed system for awake fMRI of an animal subject can be denoised using various methods such as MPPCA (Marcenko-Pastur PCA), VST, 1-D wavelet, and multivariate-wavelet. In some embodiments, the disclosed system for awake fMRI of an animal subject can be used for high resolution (e.g., 100 μm) echo planar imaging (EPI) scan for brain imaging. In some embodiments, the system for awake fMRI of an animal subject can provide a higher SNR that can be at least two times better than a commercial 4-array coil (>40K).
The present invention has been described in terms of one or more preferred embodiments, and it should be appreciated that many equivalents, alternatives, variations, and modifications, aside from those expressly stated, are possible and within the scope of the invention.
This application is based on, claims priority to, and incorporates herein by reference in its entirety U.S. Ser. No. 63/394,029 filed Aug. 1, 2022, and entitled “Awake Animal Functional MRI Mapping Platform.”
This invention was made with government support under award numbers NS124778 and NS121642 awarded by the National Institutes of Health. The government has certain rights in the invention.
Number | Date | Country | |
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63394029 | Aug 2022 | US |