Ulrich M. Scheven

In this work, we characterized the material properties of an animal model of the rotator cuff tendon using full volume datasets of both its intact and injured states by capturing internal strain behavior throughout the tendon. Our experimental setup, involving tension along the fiber direction, activated volumetric, tensile, and shear mechanisms due to the tendon's complex geometry. We implemented an approach to model inference that we refer to as variational system identification (VSI) to solve the weak form of the stress equilibrium equation using these full volume displacements. Three constitutive models were used for parameter inference: a neo-Hookean model, a modified Holzapfel-Gasser-Ogden (HGO) model with higher-order terms in the first and second invariants, and a reduced polynomial model consisting of terms based on the first, second, and fiber-related invariants. Inferred parameters were further refined using an adjoint-based partial differential equation (PDE)-constrained optimization framework. Our results show that the modified HGO model captures the tendon's deformation mechanisms with reasonable accuracy, while the neo-Hookean model fails to reproduce key internal features, particularly the shear behavior in the injured tendon. Surprisingly, the simplified polynomial model performed comparably to the modified HGO formulation using only three terms. These findings suggest that while current constitutive models do not fully replicate the complex internal mechanics of the tendon, they are capable of capturing key trends in both intact and damaged tissue, using a homogeneous modeling approach. Continued model development is needed to bridge this gap and enable clinical-grade, predictive simulations of tendon injury and repair.

In this work, we characterized the material properties of an animal model of the rotator cuff tendon using full volume datasets of both its intact and injured states by capturing internal strain behavior throughout the tendon. Our experimental setup, involving tension along the fiber direction, activated volumetric, tensile, and shear mechanisms due to the tendon's complex geometry. We implemented an approach to model inference that we refer to as variational system identification (VSI) to solve the weak form of the stress equilibrium equation using these full volume displacements. Three constitutive models were used for parameter inference: a neo-Hookean model, a modified Holzapfel-Gasser-Ogden (HGO) model with higher-order terms in the first and second invariants, and a reduced polynomial model consisting of terms based on the first, second, and fiber-related invariants. Inferred parameters were further refined using an adjoint-based partial differential equation (PDE)-constrained optimization framework. Our results show that the modified HGO model captures the tendon's deformation mechanisms with reasonable accuracy, while the neo-Hookean model fails to reproduce key internal features, particularly the shear behavior in the injured tendon. Surprisingly, the simplified polynomial model performed comparably to the modified HGO formulation using only three terms. These findings suggest that while current constitutive models do not fully replicate the complex internal mechanics of the tendon, they are capable of capturing key trends in both intact and damaged tissue, using a homogeneous modeling approach. Continued model development is needed to bridge this gap and enable clinical-grade, predictive simulations of tendon injury and repair.

Introduction Articular cartilage (AC) defects of the patellofemoral joint (PFJ) are clinically challenging and mechanically demanding. Osteochondral allograft (OCA) transplantation is the standard treatment for large cartilage injuries; however, little is known about intra-tissue mechanics after transplantation. Computational models suggest that cartilage thickness mismatch concentrates stresses at donor–recipient interfaces in OCA-treated patella, but direct experimental evidence is scarce. Local cartilage strain is closely linked to tissue health; therefore, the goal of this work was to provide a preliminary, full volume assessment of patellar cartilage mechanics before and after OCA transplantation. Methods A displacement-encoded MRI sequence was used to quantify full volume displacement and strain fields in human patellar AC before and after OCA transplantation under controlled indentation. Intact cadaveric patellae (n = 4) were prepared, with three serving as recipients and one as donor. Samples were cyclically compressed in a custom-built rig using nominal displacements of 1 and 2 mm. The complex phase data were unwrapped and converted to displacements; the Green–Lagrange strain tensor was computed using a finite element framework in FEniCS. Minimum principal strain ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="m1"> <mml:mrow> <mml:msub> <mml:mi>E</mml:mi> <mml:mi mathvariant="italic">min</mml:mi> </mml:msub> </mml:mrow> </mml:math> ) and maximum shear strain ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="m2"> <mml:mrow> <mml:msub> <mml:mi>E</mml:mi> <mml:mrow> <mml:mi>m</mml:mi> <mml:mi>a</mml:mi> <mml:mi>x</mml:mi> <mml:mi>s</mml:mi> <mml:mi>h</mml:mi> <mml:mi>e</mml:mi> <mml:mi>a</mml:mi> <mml:mi>r</mml:mi> </mml:mrow> </mml:msub> </mml:mrow> </mml:math> ) were analyzed. Donor–recipient step-off distance, representing cartilage-level geometric mismatch, was measured at the graft interface. Results Global displacement fields were similar between intact and OCA samples, with spherical indentation exhibiting through-thickness compression and lateral displacement in longitudinal and transverse directions. <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="m3"> <mml:mrow> <mml:msub> <mml:mi>E</mml:mi> <mml:mi mathvariant="italic">min</mml:mi> </mml:msub> </mml:mrow> </mml:math> localized beneath the indenter, while <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="m4"> <mml:mrow> <mml:msub> <mml:mi>E</mml:mi> <mml:mrow> <mml:mi>m</mml:mi> <mml:mi>a</mml:mi> <mml:mi>x</mml:mi> <mml:mi>s</mml:mi> <mml:mi>h</mml:mi> <mml:mi>e</mml:mi> <mml:mi>a</mml:mi> <mml:mi>r</mml:mi> </mml:mrow> </mml:msub> </mml:mrow> </mml:math> concentrated near the articular surface. OCA-transplanted samples exhibited localized changes in strain distribution near portions of the graft rim, though these features varied across samples. Top-view percentile maps highlighted redistributed high-strain regions in some OCA samples. Exploratory step-off plots showed sample-specific directional trends between geometric mismatch and donor-recipient strain differences, though these trends were not consistent across all samples. Discussion This exploratory study provides the first experimental full volume displacement and strain distributions of patellar cartilage after OCA transplantation. The localized strain variations observed after transplantation should be interpreted descriptively, given the single-donor design and sub-physiological loading. These results establish an experimental foundation for validating computational models of the donor-recipient cartilage interaction and geometric mismatch following OCA transplantation and work investigating OCA mechanics under physiological loading.

Submaximal loading during routine activities is an understudied contributor to evolving mechanics preceding acute Anterior Cruciate Ligament (ACL) injury. This study characterizes the history-dependent mechanical response of the anteromedial (AM) bundle of the ACL subjected to repeated submaximal low-strain cyclic loading and intermittent recovery periods. This loading regime represents early-stage behavior often referred to as preconditioning, which is important for achieving steady-state mechanics but also for understanding the onset of irreversible changes. Digital image correlation (DIC) reveals the development of localized inelastic deformation in regions corresponding to clinically observed acute ACL tears. Complementary repeated cycle-recovery (RCR) experiments reveal that inelastic deformation and normalized hysteresis follow a dual-regime pattern, with pronounced early-cycle attenuation followed by a linear-log response. These findings indicate that submaximal loading induces irreversible mechanical changes on short time scales and establishes a mechanistic link between physiological relevant load histories and increased site-specific susceptibility of the ACL.

Motivation: Quantitative MRI (qMRI) parameter validation with histology is often done with ex vivo fixed tissue. Freezing is another preservation method, but the effects of freezing/thawing on qMRI parameters and their correlation with histology are unknown. Goal(s): We investigated how freezing/thawing brain tissue affects myelin-sensitive qMRI properties and histology correlation. Approach: We scanned the same fresh/thawed and fresh/fixed samples and compared qMRI parameters with luxol fast blue (LFB) results. Results: qMRI values correlated well with LFB across conditions. Thawed and fixed tissues exhibited modest increases in qMRI parameters compared to fresh. Histology showed that samples did not lose tissue integrity from the freezing process. Impact: Tissue freezing is a reasonable alternative preservation method to tissue fixation for use in qMRI analysis. Brain banks that store frozen tissue could use these samples for future qMRI and histological studies.

Motivation: There is a need for better characterization of white matter lesions in Alzheimer's disease and related disorders (ADRD) to distinguish between benign lesions and destructive lesions. Goal(s): Evaluate the utility of diffusion-T2 (D-T2) 2-dimensional MR in characterizing white matter abnormalities in post-mortem ADRD samples. Approach: We scanned a D-T2 phantom (spin-echo D-T2) and post-mortem ADRC brain samples (EPI D-T2), then we computed their 2D spectras. Results: We successfully validated our D-T2 protocol with the phantom. D-T2 spectra resolved tissue components of varying T2 and diffusion values in normal and abnormal white matter, revealing more information than 1D diffusion tensor imaging ADC outcomes. Impact: The D-T2 phantom can serve as a standard for validating D-T2 imaging protocols. Applying D-T2 to assess ADRD lesions could allow for more disease-specific diagnostics with MRI.

ABSTRACT Understanding gastric physiology in rodents is critical for advancing preclinical neurogastroenterology research. However, existing techniques are often invasive, terminal, or limited in resolution. This study aims to develop a non‐invasive, standardized MRI protocol capable of capturing whole‐stomach dynamics in anesthetized rats with high spatiotemporal resolution. Experiments were performed in a 7‐T MRI system. Gadolinium‐doped test meals were prepared to enhance intraluminal contrast in T 1 ‐weighted MRI. Based on a modified multi‐slice gradient‐echo sequence, our protocol integrates respiratory gating to minimize motion artifacts, spatial saturation to improve intraluminal contrast, and slice grouping to optimize the trade‐offs between signal‐to‐noise ratio and motion sensitivity. Image acquisition was accelerated using a time‐interleaved k‐space undersampling scheme, with missing data reconstructed through k‐t interpolation. Image quality and gastric motility were quantitatively assessed. The protocol enabled successful imaging of the stomach and visualization of its quasi‐periodic dynamics in anesthetized rats. The gadolinium‐doped meal produced relatively homogeneous intraluminal contrast, allowing clear delineation of gastric anatomy, volume, and motility. The retrospectively reconstructed image exhibited high image quality and yielded reliable estimates of antral contractions, confirming the effectiveness and robustness of the k‐t interpolation method. Estimated antral contraction amplitude and velocity showed minimal deviations from the reference values, whereas contraction frequency estimation remained highly consistent and accurate. Using the accelerated imaging protocol, we imaged the entire stomach and major intestinal regions, acquiring 24 slices with an effective temporal resolution of &lt; 3 s and capturing antral contraction at ~5 cycles per minute. We established an accessible and standardized imaging protocol that encompasses contrast meal preparation, animal handling and training, and a contrast‐enhanced dynamic GI MRI acquisition and reconstruction framework. This protocol provides a comprehensive, robust, non‐invasive tool for studying gastric motility and dysmotility in rodents, offering strong potential to advance preclinical gastrointestinal motility research.

In this work, we evaluate the mechanical response of rotator cuff tendons with high-grade partial thickness tears through a recently developed full volume measurement technique that resolves through-thickness behavior. As opposed to traditional strain measurement methods, which examine surfaces of the tendon or localized two-dimensional regions, we have probed three-dimensional strains including internal locations via magnetic resonance imaging. Differences between the intact and torn states have been considered in an ex-vivo ovine model of the rotator cuff. The torn condition depicts sliding between cut/uncut tissue regions, with high shear strain concentrations at the boundaries of detached/attached tissue portions. At both submaximal and supramaximal force levels, the internal and inferior bands of the tendon show high shear strain magnitudes, which could indicate regions of high risk for tear propagation. Geometrical features which could explain strain distribution differences in their intact and torn conditions are also analyzed. Through the understanding of full volume displacement and strain distributions, our study elucidates why two-dimensional values might not represent the global behavior of the injured tendon, critical components of the Lagrangian strain tensor which have not been probed before, and important implications for surgical repairs.

PURPOSE: Validation of quantitative MRI (qMRI) parameters with histology is often done with ex vivo fixed tissue samples. Freezing is another common form of tissue preservation, but the effects of freezing and thawing tissue on myelin-sensitive quantitative MRI parameters and their correlation with histology require further analysis. METHODS: Myelin water imaging, off-resonance RF saturation magnetization transfer (MT), and selective inversion recovery MT MRI experiments were conducted on 14 fresh, thawed, and fixed sheep brain tissue samples to calculate various surrogate measures of myelin content. These measures were compared with luxol fast blue (LFB) histological stain results. RESULTS: Fresh, thawed, and fixed tissue qMRI values correlated well with LFB. Thawed and fixed tissue exhibited modest increases, between 3% and 32%, for most qMRI parameter values compared to fresh. Histology results showed that thawed samples did not lose tissue integrity from the freezing process. CONCLUSION: Freezing is a reasonable alternative tissue preservation method to fixation for use in qMRI analysis, but may differentially affect qMRI parameter values in regions with varying myelin content.

Objective: Understanding gastric physiology in rodents is critical for advancing preclinical neurogastroenterology research. However, existing techniques are often invasive, terminal, or limited in resolution. This study aims to develop a non-invasive, standardized MRI protocol capable of capturing whole-stomach dynamics in anesthetized rats with high spatiotemporal resolution. Methods: -weighted MRI. Based on a modified multi-slice gradient-echo sequence, our protocol integrates respiratory gating to minimize motion artifacts, spatial saturation to improve intraluminal contrast, and slice grouping to optimize the trade-offs between signal-to-noise ratio and motion sensitivity. Image acquisition was accelerated using a time-interleaved k-space undersampling scheme, with missing data reconstructed through k-t interpolation. Image quality and gastric motility were quantitatively assessed. Results: The protocol enabled successful imaging of the stomach and visualization of its pseudo-periodic dynamics in anesthetized rats. The gadolinium-doped meal produced relatively homogeneous intraluminal contrast, allowing clear delineation of gastric anatomy, volume, and motility. The retrospectively reconstructed image exhibited high image quality and yielded reliable estimates of antral contractions, confirming the effectiveness and robustness of k-t interpolation method. Estimated antral contraction amplitude and velocity showed minimal deviations from the reference values, whereas contraction frequency estimation remained highly consistent and accurate. Prospective acquisitions using the accelerated imaging protocol successfully imaged the entire stomach and major intestinal regions, acquiring 24 slices every < 3 s and capturing antral contraction at ∼5 cycles per minute. Conclusion: We established an accessible and standardized imaging protocol that encompasses contrast meal preparation, animal handling and training, and a contrast-enhanced dynamic GI MRI acquisition and reconstruction framework. Significance: This protocol provides a comprehensive, robust, non-invasive tool for studying gastric motility and dysmotility in rodents, offering strong potential to advance preclinical gastrointestinal motility research. Graphic Abstract: In this paper, we report a standardized, non-invasive imaging protocol that encompasses animal handling and training, contrast meal preparation, and a contrast-enhanced dynamic GI MRI acquisition and reconstruction framework for imaging whole-stomach dynamics in anesthetized rats.

Purpose: Validation of quantitative MRI (qMRI) parameters with histology is often done with ex vivo fixed tissue samples. Freezing is another common form of tissue preservation, but the effects of freezing and thawing tissue on myelin-sensitive quantitative MRI parameters and their correlation with histology require further analysis. Methods: Myelin water imaging, off-resonance RF saturation magnetization transfer (MT), and selective inversion recovery MT MRI experiments were conducted on 14 fresh, thawed, and fixed sheep brain tissue samples to calculate various surrogate measures of myelin content. These measures were compared with luxol fast blue (LFB) histological stain results. Results: Fresh, thawed, and fixed tissue qMRI values correlated well with LFB. Thawed and fixed tissue exhibited modest increases, between 3-32%, for most qMRI parameter values compared to fresh. Histology results showed that thawed samples did not lose tissue integrity from the freezing process. Conclusion: Freezing is a reasonable alternative tissue preservation method to fixation for use in qMRI analysis, but may differentially affect qMRI parameter values in regions with varying myelin content.

Histotripsy has emerged as a promising therapeutic option for liver tumors, recently gaining food and drug administration (FDA) approval for clinical use in October 2023. Preclinical in vivo histotripsy experiments primarily utilize subcutaneous ectopic murine tumor models, which fail to accurately replicate the complex immunosuppressive tumor microenvironment (TME) of liver tumors. In order to address this gap, we present the design, development, and in vivo demonstration of a miniature, electronically steerable magnetic resonance imaging (MRI)-guided histotripsy array tailored for orthotopic murine liver tumor models. This novel system integrates an 89-element phased array within a 7.0-T small animal MRI scanner, enabling precise targeting through enhanced soft tissue contrast and 3-D visualization. The targeting accuracy of the array was validated in tissue-mimicking red blood cell (RBC) phantoms, exhibiting targeting precision of $0.24~\pm ~0.1$ mm. Subsequent in vivo experiments in naïve mice demonstrated successful liver ablations, confirmed by gross morphology and histological analysis. However, the presence of grating lobes led to undesired collateral damage, highlighted by lung hemorrhages, necessitating future adjustments in the array's design. This study illustrates the foundational steps necessary for translating histotripsy experiments from subcutaneous to orthotopic models.

INTRODUCTION: Gastrointestinal (GI) magnetic resonance imaging (MRI) enables simultaneous assessment of gastric peristalsis, emptying, and intestinal filling and transit. However, GI MRI in animals typically requires anesthesia, which complicates physiology and confounds interpretation and translation to humans. This study aimed to establish GI MRI in conscious rats, and for the first time, characterize GI motor functions in awake versus anesthetized conditions. METHODS: Fourteen Sprague-Dawley rats were acclimated to remain awake, still, and minimally stressed during MRI. GI MRI was performed under both awake and anesthetized conditions following voluntary consumption of a contrast-enhanced test meal. RESULTS: Awake rats remained physiologically stable during MRI, giving rise to gastric emptying of 23.7% ± 1.4% at 48 min and robust peristaltic contractions propagating through the antrum at 0.72 ± 0.04 mm/s, with a relative amplitude of 40.7% ± 2.3% and a frequency of 5.1 ± 0.1 cycles per minute. Under anesthesia, gastric emptying was approximately halved, mainly due to a significant reduction in peristaltic contraction amplitude, rather than the change in propagation speed, whereas the contraction frequency remained unchanged. Additionally, the small intestine showed faster filling and stronger motility in awake rats. CONCLUSION: This study demonstrates the feasibility of GI MRI in awake rats and highlights notable differences in gastric and intestinal motility between awake and anesthetized states. Our protocol provides a novel and valuable framework for preclinical studies of GI physiology and pathophysiology.

Motivation: Studying ex vivo tissue requires preservation by formalin-fixation or freezing. Effects of these methods on tissue parameters compared to fresh tissue is unknown. Goal(s): We investigated how freezing/thawing and fixation affect T1, T2, and MT properties in brain tissue. We created a protocol to apply MR methods (T2-MESE, biexponential T1, qMT, ihMT, NODDI) to pathology specimens in the Michigan Alzheimer&amp;rsquo;s Disease Research Center (MADRC) repository. Approach: We scanned the same ex vivo sheep brain samples fresh, frozen/thawed, and fixed, and compared their relaxation and MT properties. Results: Effects of fixation are most prominent in white matter and especially influence T1 and T2 relaxation. Impact: Thawed tissue exhibits more similar relaxation and MT properties to fresh tissue than fixed tissue does. In MR studies that use ex vivo tissue samples, such as those correlating MR to histology, thawed tissue may be preferable to formalin-fixed.

Motivation: Direct and granular cross-species comparisons of gastric motor functions remain scarce in the literature. Goal(s): This study aims to establish functional similarities and distinctions of the stomach between humans and rats, and lay the foundation for integrating preclinical findings into clinical gastrointestinal studies. Approach: Using comparable MRI protocols, we examined the interspecies parallels and distinctions in their functions as pressure and peristaltic pumps. Results: Similarities were confirmed with high-resolution spatial maps, including intragastric pressure gradient and spatial distribution of peristaltic amplitude and frequency, despite their differences in scale. We highlighted the pronounced variance in initialization and spatial coordination of peristaltic contractions across species. Impact: This work serves as the first one to map and compare gastric motor events with comparable MRI protocols, laying the foundation for preclinical rat research to clinical translation using contrast-enhanced gastrointestinal MRI.

Introduction: Gastrointestinal (GI) magnetic resonance imaging (MRI) can simultaneously capture gastric peristalsis, emptying, and intestinal filling and transit. Performing GI MRI with animals requires anesthesia, which complicates physiology and confounds interpretation and translation from animals to humans. This study aims to enable MRI in conscious rats, and for the first time, characterize GI motor functions in awake versus anesthetized conditions. Methods: We acclimated rats to remain awake, still, and minimally stressed during MRI. We scanned 14 Sprague-Dawley rats in both awake and anesthetized conditions after voluntarily consuming a contrast-enhanced test meal. Results: Awake rats remained physiologically stable during MRI, showed gastric emptying of 23.7±1.4% after 48 minutes, and exhibited strong peristaltic contractions propagating through the antrum with a velocity of 0.72±0.04 mm/s, a relative amplitude of 40.7±2.3%, and a frequency of 5.1±0.1 cycles per minute. In the anesthetized condition, gastric emptying was about half of that in the awake condition, likely due to the effect of anesthesia in halving the amplitudes of peristaltic contractions rather than their frequency (not significantly changed) or velocity. In awake rats, the intestine filled more quickly and propulsive contractions were more occlusive. Conclusion: We demonstrated the effective acquisition and analysis of GI MRI in awake rats. Awake rats show faster gastric emptying, stronger gastric contraction with a faster propagation speed, and more effective intestinal filling and transit, compared to anesthetized rats. Our protocol is expected to benefit future preclinical studies of GI physiology and pathophysiology.

Anesthesia has been required for preclinical gastrointestinal MRI but may confound gastric physiology. This study demonstrates, for the first time, the feasibility of gastrointestinal MRI with awake rats, and reports the effects of anesthesia on gastric motor function. Results suggest that awake rats show greater rates of gastric emptying and intestinal filling, and stronger gastric and intestinal motility relative to those anesthetized. Anesthesia with 2.5% isoflurane can entirely stop muscle contraction. The methods and findings reported herein lay the foundation for using awake GI-MRI in preclinical studies of gastrointestinal function or dysfunction.

Gastric Electrical Stimulation (GES) is an FDA approved therapy for gastroparesis with unspecified working mechanisms. One plausible mechanism is that it activates the vagal afferents to engage the brain’s interoceptive network in regulating the stomach. Orientation and location-specific stimulation that targets the vagal-gastric receptors can effectively activate the brainstem. We asked whether and how this type of GES can engage interoceptive regions and modulate their interactions, especially the anterior cingulate (ACC) and insular cortices (IC), the primary visceromotor and viscerosensory processing regions, respectively. Therefore, we evaluated the functional connectivity in the rat brain before, during, and after targeted GES.

We describe a method, namely neural ordinary differential equations, to track the movement of the stomach based on dynamic and contrast-enhanced gastrointestinal MRI. This model uses a neural network to learn the continuous biomechanical process that drives the shape change of the stomach wall over the course of digestion. This method allows us to represent gastric motor events on a generic surface template of the stomach and to further reveal the pattern of gastric motility with higher specificity and resolution than are previously attainable in vivo. This method should be also applicable to other organs, such as the heart.

A novel MRI technique can visualize how the stomach accommodates, mixes, and propels food for digestion in humans and animals alike. Digital models of gastric MRI reveal the functional maps, organization, and distinction of the stomach across individuals and species. This technique holds the unique potential to advance basic and clinical studies of functional gastric disorders.

PURPOSE: To observe the growth and resolution of decompression gas bubbles in the spinal cord of live rats in real time using MRI. METHODS: We constructed an MRI-compatible pressure chamber system to visualize gas bubble dynamics in deep tissues in real time. The system pressurizes and depressurizes rodents inside an MRI scanner and monitors their respiratory rate, heart rate, and body temperature while providing gaseous anesthesia under pressure during the experiments. RESULTS: We observed the formation of decompression gas bubbles in the spinal cord of rats after compression to 7.1 bar absolute and rapid decompression inside the MRI scanner while maintaining continuous gaseous anesthesia and vital monitoring. CONCLUSION: We have shown the direct observation of decompression gas bubble formation in real time by MRI in live, anesthetized rats.

Purpose: Painful neuromas commonly develop after peripheral nerve transection, which can significantly affect patients’ quality of life. These injuries result in significant changes across the brain, also affecting regions relevant to pain. The Regenerative Peripheral Nerve Interface (RPNI), a muscle graft attached to the distal end of a transected nerve, has emerged as a promising treatment to prevent both neuroma and phantom limb pain (PLP) after limb amputation. However, the underlying central mechanisms that may be responsible for RPNI mitigation of neuroma pain and PLP remain unknown. Using resting state-functional MRI (rs-fMRI), we analyzed functional connectivity in the healthy rat brain and after nerve transection. Methods: Six male Fischer rats were randomized into three groups: RPNI, neuroma, and naïve control. The left common peroneal (CP) nerve was transected in the RPNI and neuroma groups. In the RPNI group, the transected nerve was subsequently implanted into a muscle graft. In the neuroma group, the CP nerve was secured to the surface of the biceps femoris without further treatment. At least 5 weeks post initial surgery, one neuroma-group rat and two naïve rats underwent rs-fMRI in a 7-Tesla small animal scanner. Data was analyzed using seed-based correlation analyses including the following regions of interest (ROIs): primary and secondary somatosensory (S1, S2) and motor cortices (M1, M2), cingulate (CC), retrosplenial granular (RSG) and insular (IC) cortices, and the prelimbic cortex (PrL). Behavioral testing for neuropathic pain (Tinel’s Test) was conducted at baseline, and then biweekly after surgery on all rats for 2 months. Results: Tinel’s test revealed a greater number of pain responses in the neuroma group rats compared to the RPNI group. Compared to naïve rats, the rat in the neuroma group showed an overall decreased functional connectivity across all brain ROIs mentioned above. In general, the most notable reduced connectivity values were between both the RSG and the PrL with each of the other ROIs. The lowest connectivity overall in the nerve injured rat was precisely between RSG and PrL. Larger connectivity was seen between M1 and S1, however these values were still less than those seen for naïve rats between these two regions. We expect RPNI rats will have comparable results to naïves, which would indicate that RPNIs can influence pain processing centrally resulting in subsequent mitigation of pain. Conclusion: In the current study, we show altered functional connectivity after nerve transection. RPNIs provide an appropriate environment for a transected nerve to regenerate and reinnervate, which will likely result in different functional connectivity patterns as those seen after nerve transection injury.

1) Structured Abstract Purpose To observe the growth and resolution of decompression gas bubbles in the spinal cord of live rats in real time using magnetic resonance imaging (MRI). Methods We constructed an MRI-compatible pressure chamber system to visualize gas bubble dynamics in deep tissues in real time. The system pressurizes and depressurizes rodents inside an MRI scanner and monitors their respiratory rate, heart rate, and body temperature while providing gaseous anesthesia under pressure during the experiments. Results We observed the formation of decompression gas bubbles in the spinal cord of rats after compression to 7.1 bar absolute and rapid decompression inside the MRI scanner while maintaining continuous gaseous anesthesia and vital monitoring. Conclusion We have shown the direct observation of decompression gas bubble formation in real time by MRI in live, anesthetized rats.

OBJECTIVE: Gastrointestinal magnetic resonance imaging (MRI) provides rich spatiotemporal data about the movement of the food inside the stomach, but does not directly report muscular activity on the stomach wall. Here we describe a novel approach to characterize the motility of the stomach wall that drives the volumetric changes of the ingesta. METHODS: A neural ordinary differential equation was optimized to model a diffeomorphic flow that ascribed the deformation of the stomach wall to a continuous biomechanical process. Driven by this diffeomorphic flow, the surface of the stomach progressively changes its shape over time, while preserving its topology and manifoldness. RESULTS: We tested this approach with MRI data collected from 10 rats under a lightly anesthetized condition, and demonstrated accurate characterization of gastric motor events with an error in the order of sub-millimeters. Uniquely, we characterized gastric anatomy and motility with a surface coordinate system common at both individual and group levels. Functional maps were generated to reveal the spatial, temporal, and spectral characteristics of muscle activity and its coordination across different regions. The peristalsis at the distal antrum had a dominant frequency and peak-to-peak amplitude of [Formula: see text] cycles per minute and [Formula: see text] mm, respectively. The relationship between muscle thickness and gastric motility was found to be distinct between two functional regions in the proximal and distal stomach. CONCLUSION: These results demonstrate the efficacy of using MRI to model gastric anatomy and function. SIGNIFICANCE: The proposed approach is expected to enable non-invasive and accurate mapping of gastric motility for preclinical and clinical studies.