MRI radiomics for hamstring strain injury identification and return to sport classification: a pilot study.

OBJECTIVE: To determine if MRI-based radiomics from hamstring muscles are related to injury and if the features could be used to perform a time to return to sport (RTS) classification. We hypothesize that radiomics from hamstring muscles, especially T2-weighted and diffusion tensor imaging-based features, are related to injury and can be used for RTS classification. SUBJECTS AND METHODS: MRI data from 32 athletes at the University of Wisconsin-Madison that sustained a hamstring strain injury were collected. Diffusion tensor imaging and T1- and T2-weighted images were processed, and diffusion maps were calculated. Radiomics features were extracted from the four hamstring muscles in each limb and for each MRI modality, individually. Feature selection was performed and multiple support vector classifiers were cross-validated to differentiate between involved and uninvolved limbs and perform binary (≤ or > 25 days) and multiclass (< 14 vs. 14-42 vs. > 42 days) classification of RTS. RESULT: The combination of radiomics features from all diffusion tensor imaging and T2-weighted images provided the most accurate differentiation between involved and uninvolved limbs (AUC ≈ 0.84 ± 0.16). For the binary RTS classification, the combination of all extracted radiomics offered the most accurate classification (AUC ≈ 0.95 ± 0.15). While for the multiclass RTS classification, the combination of features from all the diffusion tensor imaging maps provided the most accurate classification (weighted one vs. rest AUC ≈ 0.81 ± 0.16). CONCLUSION: This pilot study demonstrated that radiomics features from hamstring muscles are related to injury and have the potential to predict RTS.

Diffusion tensor imaging of hamstring muscles after acute strain injury and throughout recovery in collegiate athletes.

OBJECTIVE: To identify the region of interest (ROI) to represent injury and observe between-limb diffusion tensor imaging (DTI) microstructural differences in muscle following hamstring strain injury. MATERIALS AND METHODS: Participants who sustained a hamstring strain injury prospectively underwent 3T-MRI of bilateral thighs using T1, T2, and diffusion-weighted imaging at time of injury (TOI), return to sport (RTS), and 12 weeks after RTS (12wks). ROIs were using the hyperintense region on a T2-weighted sequence: edema, focused edema, and primary muscle injured excluding edema (no edema). Linear mixed-effects models were used to compare diffusion parameters between ROIs and timepoints and limbs and timepoints. RESULTS: Twenty-four participants (29 injuries) were included. A significant ROI-by-timepoint interaction was detected for all diffusivity measures. The edema and focused edema ROIs demonstrated increased diffusion at TOI compared to RTS for all diffusivity measures (p-values < 0.006), except λ1 (p-values = 0.058-0.12), and compared to 12wks (p-values < 0.02). In the no edema ROI, differences in diffusivity measures were not observed (p-values > 0.82). At TOI, no edema ROI diffusivity measures were lower than the edema ROI (p-values < 0.001) but not at RTS or 12wks (p-values > 0.69). A significant limb-by-timepoint interaction was detected for all diffusivity measures with increased diffusion in the involved limb at TOI (p-values < 0.001) but not at RTS or 12wks (p-values > 0.42). Significant differences in fractional anisotropy over time or between limbs were not detected. CONCLUSION: Hyperintensity on T2-weighted imaging used to define the injured region holds promise in describing muscle microstructure following hamstring strain injury by demonstrating between-limb differences at TOI but not at follow-up timepoints.

Peripheral inflammation is associated with micro-structural and functional connectivity changes in depression-related brain networks.

Inflammation is associated with depressive symptoms and innate immune mechanisms are likely causal in some cases of major depression. Systemic inflammation also perturbs brain function and microstructure, though how these are related remains unclear. We recruited N = 46 healthy controls, and N = 83 depressed cases stratified by CRP (> 3 mg/L: N = 33; < 3 mg/L: N = 50). All completed clinical assessment, venous blood sampling for C-reactive protein (CRP) assay, and brain magnetic resonance imaging (MRI). Micro-structural MRI parameters including proton density (PD), a measure of tissue water content, were measured at 360 cortical and 16 subcortical regions. Resting-state fMRI time series were correlated to estimate functional connectivity between individual regions, as well as the sum of connectivity (weighted degree) of each region. Multiple tests for regional analysis were controlled by the false discovery rate (FDR = 5%). We found that CRP was significantly associated with PD in precuneus, posterior cingulate cortex (pC/pCC) and medial prefrontal cortex (mPFC); and with functional connectivity between pC/pCC, mPFC and hippocampus. Depression was associated with reduced weighted degree of pC/pCC, mPFC, and other nodes of the default mode network (DMN). Thus CRP-related increases in proton density-a plausible marker of extracellular oedema-and changes in functional connectivity were anatomically co-localised with DMN nodes that also demonstrated significantly reduced hubness in depression. We suggest that effects of peripheral inflammation on DMN node micro-structure and connectivity may mediate inflammatory effects on depression.

A method to remove the influence of fixative concentration on postmortem T2 maps using a kinetic tensor model.

Formalin fixation has been shown to substantially reduce T2 estimates, primarily driven by the presence of fixative in tissue. Prior to scanning, post-mortem samples are often placed into a fluid that has more favourable imaging properties. This study investigates whether there is evidence for a change in T2 in regions close to the tissue surface due to fixative outflux into this surrounding fluid. Furthermore, we investigate whether a simulated spatial map of fixative concentration can be used as a confound regressor to reduce T2 inhomogeneity. To achieve this, T2 maps and diffusion tensor estimates were obtained in 14 whole, formalin-fixed post-mortem brains placed in Fluorinert approximately 48 hr prior to scanning. Seven brains were fixed with 10% formalin and seven brains were fixed with 10% neutral buffered formalin (NBF). Fixative outflux was modelled using a proposed kinetic tensor (KT) model, which incorporates voxelwise diffusion tensor estimates to account for diffusion anisotropy and tissue-specific diffusion coefficients. Brains fixed with 10% NBF revealed a spatial T2 pattern consistent with modelled fixative outflux. Confound regression of fixative concentration reduced T2 inhomogeneity across both white and grey matter, with the greatest reduction attributed to the KT model versus simpler models of fixative outflux. No such effect was observed in brains fixed with 10% formalin. Correlations between the transverse relaxation rate R2 and ferritin/myelin proteolipid protein (PLP) histology lead to an increased similarity for the relationship between R2 and PLP for the two fixative types after KT correction.

PET Image Quality Improvement for Simultaneous PET/MRI with a Lightweight MRI Surface Coil.

Background During simultaneous PET/MRI, flexible MRI surface coils that lay on the patient are often omitted from PET attenuation correction processing, leading to quantification bias in PET images. Purpose To identify potential PET image quality improvement by using a recently developed lightweight MRI coil technology for the anterior array (AA) surface coil in both a phantom and in vivo study. Materials and Methods A phantom study and a prospective in vivo study were performed with a PET/CT scanner under three conditions: (a) no MRI surface coil (standard of reference), (b) traditional AA coil, and (c) lightweight AA coil. AA coils were not used in attenuation correction processing to emulate clinical PET/MRI. For the phantom study, PET images were reconstructed with and without time of flight (TOF) to assess quantification accuracy and uniformity. The in vivo study consisted of 10 participants (mean age, 66 years ± 10 [standard deviation]; six men) referred for a PET/CT oncologic examination who had undergone imaging between October 2019 and February 2020. Assessment of image quantification bias (defined as the standard error of the mean values) was conducted by comparing mean liver region of interest standardized uptake values with the no-coil standard of reference. A Wilcoxon signed-rank test was used to establish significance. Results For TOF and non-TOF, respectively, the phantom study revealed a mean PET quantification bias of -9.0% and -8.6% with the traditional AA coil and a mean PET quantification bias of -4.3% and -4.0% with the lightweight AA coil. The coefficients of variation reduced from 4.3% and 6.2% with the traditional AA coil to 2.1% and 2.7% with the lightweight AA coil, which demonstrated a homogeneity benefit from the lightweight coil that was greater with, versus without, TOF reconstruction. For the in vivo study, the mean liver standardized uptake value error was -5.9% with the traditional AA coil (P = .002 vs no coil) and -2.4% with the lightweight AA coil (P = .004 vs no coil). Conclusion The lightweight anterior array coil reduced PET image quantification bias by more than 50% compared with the traditional coil. Using the lightweight coil and performing time of flight-based reconstruction each reduced the variation of error. © RSNA, 2020 Online supplemental material is available for this article.

Changes in Endogenous Dopamine Induced by Methylphenidate Predict Functional Connectivity in Nonhuman Primates.

Dopamine (DA) levels in the striatum are increased by many therapeutic drugs, such as methylphenidate (MPH), which also alters behavioral and cognitive functions thought to be controlled by the PFC dose-dependently. We linked DA changes and functional connectivity (FC) using simultaneous [18F]fallypride PET and resting-state fMRI in awake male rhesus monkeys after oral administration of various doses of MPH. We found a negative correlation between [18F]fallypride nondisplaceable binding potential (BPND) and MPH dose in the head of the caudate (hCd), demonstrating increased extracellular DA resulting from MPH administration. The decreased BPND was negatively correlated with FC between the hCd and the PFC. Subsequent voxelwise analyses revealed negative correlations with FC between the hCd and the dorsolateral PFC, hippocampus, and precuneus. These results, showing that MPH-induced changes in DA levels in the hCd predict resting-state FC, shed light on a mechanism by which changes in striatal DA could influence function in the PFC.SIGNIFICANCE STATEMENT Dopamine transmission is thought to play an essential role in shaping large scale-neural networks that underlie cognitive functions. It is the target of therapeutic drugs, such as methylphenidate (Ritalin), which blocks the dopamine transporter, thereby increasing extracellular dopamine levels. Methylphenidate is used extensively to treat attention deficit hyperactivity disorder, even though its effects on cognitive functions and their underlying neural mechanisms are not well understood. To date, little is known about the link between changes in dopamine levels and changes in functional brain organization. Using simultaneous PET/MR imaging, we show that methylphenidate-induced changes in endogenous dopamine levels in the head of the caudate predict changes in resting-state functional connectivity between this structure and the prefrontal cortex, precuneus, and hippocampus.

Advancing RF pulse design using an open-competition format: Report from the 2015 ISMRM challenge.

PURPOSE: To advance the best solutions to two important RF pulse design problems with an open head-to-head competition. METHODS: Two sub-challenges were formulated in which contestants competed to design the shortest simultaneous multislice (SMS) refocusing pulses and slice-selective parallel transmission (pTx) excitation pulses, subject to realistic hardware and safety constraints. Short refocusing pulses are needed for spin echo SMS imaging at high multiband factors, and short slice-selective pTx pulses are needed for multislice imaging in ultra-high field MRI. Each sub-challenge comprised two phases, in which the first phase posed problems with a low barrier of entry, and the second phase encouraged solutions that performed well in general. The Challenge ran from October 2015 to May 2016. RESULTS: The pTx Challenge winners developed a spokes pulse design method that combined variable-rate selective excitation with an efficient method to enforce SAR constraints, which achieved 10.6 times shorter pulse durations than conventional approaches. The SMS Challenge winners developed a time-optimal control multiband pulse design algorithm that achieved 5.1 times shorter pulse durations than conventional approaches. CONCLUSION: The Challenge led to rapid step improvements in solutions to significant problems in RF excitation for SMS imaging and ultra-high field MRI. Magn Reson Med 78:1352-1361, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Optimal echo time for functional MRI of the infant brain identified in response to noxious stimulation.

PURPOSE: Blood oxygen level dependent (BOLD) brain activity, measured using functional MRI (fMRI), is dependent on the echo time (TE) and the reversible spin-spin relaxation time constant ( T2*) that describes the decay of transverse magnetization. Use of the optimal TE during fMRI experiments allows maximal sensitivity to BOLD to be achieved. Reports that T2* values are longer in infants (due to higher water concentrations and lower lipid content) have led to the use of longer TEs during infant fMRI experiments; however, the optimal TE has not been established. METHODS: In this study, acute experimental mildly noxious stimuli were applied to the heel in 12 term infants (mean gestational age = 40 weeks, mean postnatal age = 3 days); and the percentage change in BOLD activity was calculated across a range of TEs, from 30 to 70 ms, at 3 Tesla. In addition, T2* maps of the whole brain were collected in seven infants. RESULTS: The maximal change in BOLD occurred at a TE of 52 ms, and the average T2* across the whole brain was 99 ms. CONCLUSION: A TE of approximately 50 ms is recommended for use in 3T fMRI investigations in term infants. Magn Reson Med 78:625-631, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

Data-driven optimized flip angle selection for T1 estimation from spoiled gradient echo acquisitions.

PURPOSE: Define criteria for selection of optimal flip angle sets for T1 estimation and evaluate effects on T1 mapping. THEORY AND METHODS: Flip angle sets for spoiled gradient echo-based T1 mapping were selected by minimizing T1 estimate variance weighted by the joint density of M0 and T1 in an initial acquisition. The effect of optimized flip angle selection on T1 estimate error was measured using simulations and experimental data in the human and rat brain. RESULTS: For two-point acquisitions, optimized angle sets were similar to those proposed by other groups and, therefore, performed similarly. For multipoint acquisitions, optimal angle sets for T1 mapping in the brain consisted of a repetition of two angles. Implementation of optimal angles reduced T1 estimate variance by 30-40% compared with a multipoint acquisition using a range of angles. Performance of the optimal angle set was equivalent to that of a repetition of the two-angle set selected using criteria proposed by other researchers. CONCLUSION: Repetition of two carefully selected flip angles notably improves the precision of resulting T1 estimates compared with acquisitions using a range of flip angles. This work provides a flexible and widely applicable optimization method of particular use for those who repeatedly perform T1 estimation. Magn Reson Med 76:792-802, 2016. © 2015 Wiley Periodicals, Inc.

MPnRAGE: A technique to simultaneously acquire hundreds of differently contrasted MPRAGE images with applications to quantitative T1 mapping.

PURPOSE: To introduce a new technique called MPnRAGE, which produces hundreds of images with different T1 contrasts and a B1 corrected T1 map. THEORY AND METHODS: An interleaved three-dimensional radial k-space trajectory with a sliding window reconstruction is used in conjunction with magnetization preparation pulses. This work modifies the SNAPSHOT-FLASH T1 fitting equations for radial imaging with view-sharing and develops a new rapid B1 correction procedure. MPnRAGE is demonstrated in phantoms and volunteers, including two volunteers with eight scans each and eight volunteers with two scans each. T1 values from MPnRAGE were compared with those from fast spin echo inversion recovery (FSE-IR) in phantoms and a healthy human brain at 3 Tesla (T). RESULTS: The T1 fit for human white and gray matter was T1MPnRAGE = 1.00 · T1FSE-IR + 24 ms, r(2) = 0.990. Voxel-wise coefficient of variation in T1 measurements across eight time points was between 0.02 and 0.08. Region of interest-based T1 values were reproducible to within 2% and agree well with literature values. CONCLUSION: In the same amount of time as a traditional MPRAGE exam (7.5 min), MPnRAGE was shown to produce hundreds of images with alternate T1 contrasts as well as an accurate and reproducible T1 map that is robust to B1 errors.

Rapid multicomponent T2 analysis of the articular cartilage of the human knee joint at 3.0T.

PURPOSE: To determine the feasibility of using multicomponent-driven equilibrium single-shot observation of T1 and T2 (mcDESPOT) for evaluating the human knee joint at 3.0T and to investigate depth-dependent and regional-dependent variations in multicomponent T2 parameters within articular cartilage. MATERIALS AND METHODS: mcDESPOT was performed on the knee joint of 10 asymptomatic volunteers at 3.0T. Single-component T2 relaxation time (T2single ), multicomponent T2 relaxation time for water tightly bound to proteoglycan (T2PG ) and bulk water loosely bound to the macromolecular matrix (T2BW ), and fraction of water tightly bound to proteoglycan (FPG ) were measured in eight cartilage subsections and within the superficial and deep layers of patellar cartilage. Statistical analysis was used to investigate depth-dependent and regional-dependent variations in parameters. RESULTS: There was lower (P = 0.001) T2single and T2PG and higher (P < 0.001) FPG in the deep than superficial layer of patellar cartilage. There was higher (P < 0.001) FPG on the weight-bearing surfaces than nonweight-bearing surfaces. There was higher (P < 0.001) T2single , T2PG , and T2BW on the trochlea and posterior medial and lateral femoral condyles than the patella, central medial and lateral femoral condyles, and medial and lateral tibia plateaus. CONCLUSION: Multicomponent T2 parameters of the articular cartilage of the human knee joint can be measured at 3.0T using mcDESPOT and show depth-dependent and regional-dependent variations.

Titer and product affect the distribution of gene expression after intraputaminal convection-enhanced delivery.

BACKGROUND: The efficacy and safety of intracerebral gene therapy for brain disorders like Parkinson's disease depends on the appropriate distribution of gene expression. OBJECTIVES: To assess whether the distribution of gene expression is affected by vector titer and protein type. METHODS: Four adult macaque monkeys seronegative for adeno-associated virus 5 (AAV5) received a 30-µl inoculation of a high- or a low-titer suspension of AAV5 encoding glial cell line-derived neurotrophic factor (GDNF) or green fluorescent protein (GFP) in the right and left ventral postcommissural putamen. The inoculations were conducted using convection-enhanced delivery and intraoperative MRI (IMRI). RESULTS: IMRI confirmed targeting and infusion cloud irradiation from the catheter tip into the surrounding area. A postmortem analysis 6 weeks after surgery revealed GFP and GDNF expression ipsilateral to the injection site that had a titer-dependent distribution. GFP and GDNF expression was also observed in fibers in the substantia nigra (SN) pars reticulata (pr), demonstrating anterograde transport. Few GFP-positive neurons were present in the SN pars compacta (pc), possibly by direct retrograde transport of the vector. GDNF was present in many neurons of the SNpc and SNpr. CONCLUSIONS: After controlling for target and infusate volume, the intracerebral distribution of the gene product was affected by the vector titer and product biology.

Relationships between quantitative magnetic resonance imaging measures at the time of return to sport and clinical outcomes following acute hamstring strain injury.

Hamstring strain injuries (HSI) are a common occurrence in athletics and complicated by high rates of reinjury. Evidence of remaining injury observed on magnetic resonance imaging (MRI) at the time of return to sport (RTS) may be associated with strength deficits and prognostic for reinjury, however, conventional imaging has failed to establish a relationship. Quantitative measure of muscle microstructure using diffusion tensor imaging (DTI) may hold potential for assessing a possible association between injury-related structural changes and clinical outcomes. The purpose of this study was to determine the association of RTS MRI-based quantitative measures, such as edema volume, muscle volume, and DTI metrics, with clinical outcomes (i.e., strength and reinjury) following HSI. Spearman's correlations and Firth logistic regressions were used to determine relationships in between-limb imaging measures and between-limb eccentric strength and reinjury status, respectively. Twenty injuries were observed, with four reinjuries. At the time of RTS, between-limb differences in eccentric hamstring strength were significantly associated with principal effective diffusivity eigenvalue λ1 (r = -0.64, p = 0.003) and marginally associated with mean diffusivity (r = -0.46, p = 0.056). Significant relationships between other MRI-based measures of morphology and eccentric strength were not detected, as well as between any MRI-based measure and reinjury status. In conclusion, this preliminary evidence indicates DTI may track differences in hamstring muscle microstructure, not captured by conventional imaging at the whole muscle level, that relate to eccentric strength.

Association of quantitative diffusion tensor imaging measures with time to return to sport and reinjury incidence following acute hamstring strain injury.

Hamstring strain injuries (HSI) are a common occurrence in athletics and complicated by limited prognostic indicators and high rates of reinjury. Assessment of injury characteristics at the time of injury (TOI) may be used to manage athlete expectations for time to return to sport (RTS) and mitigate reinjury risk. Magnetic resonance imaging (MRI) is routinely used in soft tissue injury management, but its prognostic value for HSI is widely debated. Recent advancements in musculoskeletal MRI, such as diffusion tensor imaging (DTI), have allowed for quantitative measures of muscle microstructure assessment. The purpose of this study was to determine the association of TOI MRI-based measures, including the British Athletic Muscle Injury Classification (BAMIC) system, edema volume, and DTI metrics, with time to RTS and reinjury incidence. Negative binomial regressions and generalized estimating equations were used to determine relationships between imaging measures and time to RTS and reinjury, respectively. Twenty-six index injuries were observed, with five recorded reinjuries. A significant association was not detected between BAMIC score and edema volume at TOI with days to RTS (p-values ≥ 0.15) or reinjury (p-values ≥ 0.13). Similarly, a significant association between DTI metrics and days to RTS was not detected (p-values ≥ 0.11). Although diffusivity metrics are expected to increase following injury, decreased values were observed in those who reinjured (mean diffusivity, p = 0.016; radial diffusivity, p = 0.02; principal effective diffusivity eigenvalues, p-values = 0.007-0.057). Additional work to further understand the directional relationship observed between DTI metrics and reinjury status and the influence of external factors is warranted.

Attenuation correction and truncation completion for breast PET/MR imaging using deep learning.

Objective. Simultaneous PET/MR scanners combine the high sensitivity of MR imaging with the functional imaging of PET. However, attenuation correction of breast PET/MR imaging is technically challenging. The purpose of this study is to establish a robust attenuation correction algorithm for breast PET/MR images that relies on deep learning (DL) to recreate the missing portions of the patient's anatomy (truncation completion), as well as to provide bone information for attenuation correction from only the PET data.Approach. Data acquired from 23 female subjects with invasive breast cancer scanned with18F-fluorodeoxyglucose PET/CT and PET/MR localized to the breast region were used for this study. Three DL models, U-Net with mean absolute error loss (DLMAE) model, U-Net with mean squared error loss (DLMSE) model, and U-Net with perceptual loss (DLPerceptual) model, were trained to predict synthetic CT images (sCT) for PET attenuation correction (AC) given non-attenuation corrected (NAC) PETPET/MRimages as inputs. The DL and Dixon-based sCT reconstructed PET images were compared against those reconstructed from CT images by calculating the percent error of the standardized uptake value (SUV) and conducting Wilcoxon signed rank statistical tests.Main results. sCT images from the DLMAEmodel, the DLMSEmodel, and the DLPerceptualmodel were similar in mean absolute error (MAE), peak-signal-to-noise ratio, and normalized cross-correlation. No significant difference in SUV was found between the PET images reconstructed using the DLMSEand DLPerceptualsCTs compared to the reference CT for AC in all tissue regions. All DL methods performed better than the Dixon-based method according to SUV analysis.Significance. A 3D U-Net with MSE or perceptual loss model can be implemented into a reconstruction workflow, and the derived sCT images allow successful truncation completion and attenuation correction for breast PET/MR images.

Cyclotron production of 43Sc and 44gSc from enriched 42CaO, 43CaO, and 44CaO targets.

Introduction: 43Sc and 44gSc are both positron-emitting radioisotopes of scandium with suitable half-lives and favorable positron energies for clinical positron emission tomography (PET) imaging. Irradiation of isotopically enriched calcium targets has higher cross sections compared to titanium targets and higher radionuclidic purity and cross sections than natural calcium targets for reaction routes possible on small cyclotrons capable of accelerating protons and deuterons. Methods: In this work, we investigate the following production routes via proton and deuteron bombardment on CaCO3 and CaO target materials: 42Ca(d,n)43Sc, 43Ca(p,n)43Sc, 43Ca(d,n)44gSc, 44Ca(p,n)44gSc, and 44Ca(p,2n)43Sc. Radiochemical isolation of the produced radioscandium was performed with extraction chromatography using branched DGA resin and apparent molar activity was measured with the chelator DOTA. The imaging performance of 43Sc and 44gSc was compared with 18F, 68Ga, and 64Cu on two clinical PET/CT scanners. Discussion: The results of this work demonstrate that proton and deuteron bombardment of isotopically enriched CaO targets produce high yield and high radionuclidic purity 43Sc and 44gSc. Laboratory capabilities, circumstances, and budgets are likely to dictate which reaction route and radioisotope of scandium is chosen.

Quantifying changes in local basal ganglia structural connectivity in the 6-hydroxydopamine model of Parkinson's Disease using correlational tractography.

In recent years, tractography based on diffusion magnetic resonance imaging (dMRI) has become a popular tool for studying microstructural changes resulting from brain diseases like Parkinson's Disease (PD). Quantitative anisotropy (QA) is a parameter that is used in deterministic fiber tracking as a measure of connection between brain regions. It remains unclear, however, if microstructural changes caused by lesioning the median forebrain bundle (MFB) to create a Parkinsonian rat model can be resolved using tractography based on ex-vivo diffusion MRI. This study aims to fill this gap and enable future mechanistic research on structural changes of the whole brain network rodent models of PD. Specifically, it evaluated the ability of correlational tractography to detect structural changes in the MFB of 6-hydroxydopamine (6-OHDA) lesioned rats. The findings reveal that correlational tractography can detect structural changes in lesioned MFB and differentiate between the 6-OHDA and control groups. Imaging results are supported by behavioral and histological evidence demonstrating that 6-OHDA lesioned rats were indeed Parkinsonian. The results suggest that QA and correlational tractography is appropriate to examine local structural changes in rodent models of neurodegenerative disease. More broadly, we expect that similar techniques may provide insight on how disease alters structure throughout the brain, and as a tool to optimize therapeutic interventions.

Vagus nerve stimulation in the non-human primate: implantation methodology, characterization of nerve anatomy, target engagement and experimental applications.

BACKGROUND: Vagus nerve stimulation (VNS) is a FDA approved therapy regularly used to treat a variety of neurological disorders that impact the central nervous system (CNS) including epilepsy and stroke. Putatively, the therapeutic efficacy of VNS results from its action on neuromodulatory centers via projections of the vagus nerve to the solitary tract nucleus. Currently, there is not an established large animal model that facilitates detailed mechanistic studies exploring how VNS impacts the function of the CNS, especially during complex behaviors requiring motor action and decision making. METHODS: We describe the anatomical organization, surgical methodology to implant VNS electrodes on the left gagus nerve and characterization of target engagement/neural interface properties in a non-human primate (NHP) model of VNS that permits chronic stimulation over long periods of time. Furthermore, we describe the results of pilot experiments in a small number of NHPs to demonstrate how this preparation might be used in an animal model capable of performing complex motor and decision making tasks. RESULTS: VNS electrode impedance remained constant over months suggesting a stable interface. VNS elicited robust activation of the vagus nerve which resulted in decreases of respiration rate and/or partial pressure of carbon dioxide in expired air, but not changes in heart rate in both awake and anesthetized NHPs. CONCLUSIONS: We anticipate that this preparation will be very useful to study the mechanisms underlying the effects of VNS for the treatment of conditions such as epilepsy and depression, for which VNS is extensively used, as well as for the study of the neurobiological basis underlying higher order functions such as learning and memory.

Simultaneous variable flip angle-actual flip angle imaging method for improved accuracy and precision of three-dimensional T1 and B1 measurements.

A new time-efficient and accurate technique for simultaneous mapping of T(1) and B(1) is proposed based on a combination of the actual flip angle (FA) imaging and variable FA methods. Variable FA-actual FA imaging utilizes a single actual FA imaging and one or more spoiled gradient-echo acquisitions with a simultaneous nonlinear fitting procedure to yield accurate T(1)/B(1) maps. The advantage of variable FA-actual FA imaging is high accuracy at either short T(1) times or long repetition times in the actual FA imaging sequence. Simulations show this method is accurate to 0.03% in FA and 0.07% in T(1) for ratios of repetition time to T1 time over the range of 0.01-0.45. We show for the case of brain imaging that it is sufficient to use only one small FA spoiled gradient-echo acquisition, which results in reduced spoiling requirements and a significant scan time reduction compared to the original variable FA method. In vivo validation yielded high-quality 3D T(1) maps and T(1) measurements within 10% of previously published values and within a clinically acceptable scan time. The variable FA-actual FA imaging method will increase the accuracy and clinical feasibility of many quantitative MRI methods requiring T(1)/B(1) mapping such as dynamic contrast enhanced perfusion and quantitative magnetization transfer imaging.