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BackgroundMultiparametric magnetic resonance imaging (mpMRI) improves detection of clinically significant prostate cancer (csPCa), but the subjective Prostate Imaging Reporting and Data System (PI-RADS) system and quantitative apparent diffusion coefficient (ADC) are inconsistent. Restriction spectrum imaging (RSI) is an advanced diffusion-weighted MRI technique that yields a quantitative imaging biomarker for csPCa called the RSI restriction score (RSIrs).ObjectiveTo evaluate RSIrs for automated patient-level detection of csPCa.Design setting and participantsWe retrospectively studied all patients (n=151) who underwent 3 T mpMRI and RSI (a 2-min sequence on a clinical scanner) for suspected prostate cancer at University of California San Diego during 2017-2019 and had prostate biopsy within 180 d of MRI.InterventionWe calculated the maximum RSIrs and minimum ADC within the prostate, and obtained PI-RADS v2.1 from medical records.Outcome measurements and statistical analysisWe compared the performance of RSIrs, ADC, and PI-RADS for the detection of csPCa (grade group ≥2) on the best available histopathology (biopsy or prostatectomy) using the area under the curve (AUC) with two-tailed α=0.05. We also explored whether the combination of PI-RADS and RSIrs might be superior to PI-RADS alone and performed subset analyses within the peripheral and transition zones.Results and limitationsAUC values for ADC, RSIrs, and PI-RADS were 0.48 (95% confidence interval: 0.39, 0.58), 0.78 (0.70, 0.85), and 0.77 (0.70, 0.84), respectively. RSIrs and PI-RADS were each superior to ADC for patient-level detection of csPCa (p&nbsp

Purpose:Diffusion-weighted MRI (DW-MRI) is a contrast-free modality that has demonstrated ability to discriminate between predefined benign and malignant breast lesions. However, how well DW-MRI discriminates cancer from all other breast tissue voxels in a clinical setting is unknown. Here we explore the voxelwise ability to distinguish cancer from healthy breast tissue using signal contributions from the newly developed three-component multi-b-value DW-MRI model.Experimental Design:Patients with pathology-proven breast cancer from two datasets (n = 81 and n = 25) underwent multi-b-value DW-MRI. The three-component signal contributions C1 and C2 and their product, C1C2, and signal fractions F1, F2, and F1F2 were compared with the image defined on maximum b-value (DWImax), conventional apparent diffusion coefficient (ADC), and apparent diffusion kurtosis (Kapp). The ability to discriminate between cancer and healthy breast tissue was assessed by the false-positive rate given a sensitivity of 80% (FPR80) and ROC AUC.Results:Mean FPR80 for both datasets was 0.016 [95% confidence interval (CI), 0.008–0.024] for C1C2, 0.136 (95% CI, 0.092–0.180) for C1, 0.068 (95% CI, 0.049–0.087) for C2, 0.462 (95% CI, 0.425–0.499) for F1F2, 0.832 (95% CI, 0.797–0.868) for F1, 0.176 (95% CI, 0.150–0.203) for F2, 0.159 (95% CI, 0.114–0.204) for DWImax, 0.731 (95% CI, 0.692–0.770) for ADC, and 0.684 (95% CI, 0.660–0.709) for Kapp. Mean ROC AUC for C1C2 was 0.984 (95% CI, 0.977–0.991).Conclusions:The C1C2 parameter of the three-component model yields a clinically useful discrimination between cancer and healthy breast tissue, superior to other DW-MRI methods and obliviating predefining lesions. This novel DW-MRI method may serve as noncontrast alternative to standard-of-care dynamic contrast-enhanced MRI.

Mean (95% CI) for all performance measures the U.S. dataset (Supplementary Table S1) and European dataset (Supplementary Table S2). Median (interquartile range) for average signal of the cancer and control regions of interests (ROIs) for both datasets combined (Supplementary Table S3).

Probability density colormaps for the three-component model given C1 and C2 for all voxels per patient for (A.) cancer (cancer ROI) and (B.) healthy breast tissue (control ROI).

Probability density colormaps for the three-component model given C1 and C2 for all voxels per patient for (A.) cancer (cancer ROI) and (B.) healthy breast tissue (control ROI).

Probability density colormaps for the three-component model given C1 and C2 for all voxels per patient for (A.) cancer (cancer ROI) and (B.) healthy breast tissue (control ROI).

One promising approach for mapping CMRO(2) is dual-calibrated functional MRI (dc-fMRI). This method exploits the Fick Principle to combine estimates of CBF from ASL, and OEF derived from BOLD-ASL measurements during arterial O(2) and CO(2) modulations. Multiple gas modulations are required to decouple OEF and deoxyhemoglobin-sensitive blood volume. We propose an alternative single gas calibrated fMRI framework, integrating a model of oxygen transport, that links blood volume and CBF to OEF and creates a mapping between the maximum BOLD signal, CBF and OEF (and CMRO(2)). Simulations demonstrated the method’s viability within physiological ranges of mitochondrial oxygen pressure, P(m)O(2), and mean capillary transit time. A dc-fMRI experiment, performed on 20 healthy subjects using O(2) and CO(2) challenges, was used to validate the approach. The validation conveyed expected estimates of model parameters (e.g., low P(m)O(2)), with spatially uniform OEF maps (grey matter, GM, OEF spatial standard deviation ≈ 0.13). GM OEF estimates obtained with hypercapnia calibrated fMRI correlated with dc-fMRI (r = 0.65, p = 2·10(−3)). For 12 subjects, OEF measured with dc-fMRI and the single gas calibration method were correlated with whole-brain OEF derived from phase measures in the superior sagittal sinus (r = 0.58, p = 0.048; r = 0.64, p = 0.025 respectively). Simplified calibrated fMRI using hypercapnia holds promise for clinical application.

PURPOSE: To develop a multicompartmental signal model for whole-body diffusion-weighted imaging (DWI) and apply it to study the diffusion properties of normal tissue and metastatic prostate cancer bone lesions in vivo. MATERIALS AND METHODS: This prospective study (ClinicalTrials.gov: NCT03440554) included 139 men with prostate cancer (mean age, 70 years ± 9 [SD]). Multicompartmental models with two to four tissue compartments were fit to DWI data from whole-body scans to determine optimal compartmental diffusion coefficients. Bayesian information criterion (BIC) and model-fitting residuals were calculated to quantify model complexity and goodness of fit. Diffusion coefficients for the optimal model (having lowest BIC) were used to compute compartmental signal-contribution maps. The signal intensity ratio (SIR) of bone lesions to normal-appearing bone was measured on these signal-contribution maps and on conventional DWI scans and compared using paired t tests (α = .05). Two-sample t tests (α = .05) were used to compare compartmental signal fractions between lesions and normal-appearing bone. RESULTS: Lowest BIC was observed from the four-compartment model, with optimal compartmental diffusion coefficients of 0, 1.1 × 10(−3), 2.8 × 10(-3), and >3.0 ×10(-2) mm(2)/sec. Fitting residuals from this model were significantly lower than from conventional apparent diffusion coefficient mapping (P < .001). Bone lesion SIR was significantly higher on signal-contribution maps of model compartments 1 and 2 than on conventional DWI scans (P < .008). The fraction of signal from compartments 2, 3, and 4 was also significantly different between metastatic bone lesions and normal-appearing bone tissue (P ≤ .02). CONCLUSION: The four-compartment model best described whole-body diffusion properties. Compartmental signal contributions from this model can be used to examine prostate cancer bone involvement. Keywords: Whole-Body MRI, Diffusion-weighted Imaging, Restriction Spectrum Imaging, Diffusion Signal Model, Bone Metastases, Prostate Cancer Clinical trial registration no. NCT03440554 Supplemental material is available for this article. © RSNA, 2023 See also commentary by Margolis in this issue.

OBJECTIVES Clinical assessment of uterine artery (UtA) hemodynamics is currently limited to Doppler ultrasound (US) velocimetry. We have demonstrated previously the feasibility of applying four-dimensional (4D) flow magnetic resonance imaging (MRI) to evaluate UtA hemodynamics during pregnancy, allowing flow quantification of the entire course of the vessel. In this study, we sought to further validate the physiological relevance of 4D flow MRI measurement of UtA blood flow by exploring its association with pregnancy outcome relative to US-based metrics. METHODS Recruited into this prospective, cross-sectional study were 87 women with a singleton pregnancy who underwent 4D flow MRI between May 2016 and April 2019 to measure the UtA pulsatility index (MRI-PI) and blood flow rate (MRI-flow, in mL/min). UtA-PI was also measured using US (US-PI). The primary outcome was a composite (COMP) of pre-eclampsia (PE) and/or small-for-gestational-age (SGA) neonate, and secondary outcomes were PE and SGA neonate individually. We assessed the ability of MRI-flow, MRI-PI and US-PI to distinguish between outcomes, and evaluated whether MRI-flow changed as gestation progressed. RESULTS Following 4D flow postprocessing and exclusions from the analysis, 74 women had 4D flow MRI data analyzed for both UtAs. Of these, 18 developed a COMP outcome: three developed PE only, 11 had a SGA neonate only and four had both. A comparison of the COMP group vs the no-COMP group found no differences in maternal age, body mass index, nulliparity, gravidity or race. For 66 of the 74 subjects, US data were also available. In these subjects, both median MRI-PI (0.95 vs 0.70; P

To date, the accuracy and variability of diffusion-weighted MRI (DW-MRI) metrics have been reported in a limited number of scanner/protocol/coil combinations.To evaluate the reproducibility of DW-MRI estimates across multiple scanners and DW-MRI protocols and to assess the effects of using an 8-channel vs. 16-channel breast coil in a breast phantom.Prospective.Breast phantom containing tubes of water and differing polyvinylpyrrolidone (PVP) concentrations with apparent diffusion coefficients (ADCs) matching breast tissue.3 T (three standard and one wide bore), three DW-MRI single-shot echo planar imaging protocols of varying acquired spatial resolution.Accuracy of estimated ADCs was assessed using percent differences (PD) relative to nuclear magnetic resonance spectroscopy-derived reference values. Coefficients of variation (CV) were calculated to determine variation across scanners. CVs based on the median standard deviation (CVTwo-way repeated measures analysis of variance and post hoc tests were used to evaluate differences in ADC, CV, and CVADCs were within 11% (interquartile range [IQR] 7%) of reference values and significantly improved to 2% (IQR 7%) after normalization to an internal water reference. Normalization significantly reduced interscanner variability of ADC estimates from 7% to 4%. DW-MRI protocol did not affect ADC accuracy; however, the clinical and higher-resolution clinical protocols resulted in the greatest (9%) and least (6%) interscanner variability, respectively. The 8- and 16-channel receive coils yielded similar accuracy (PD: 12% vs. 16%) and precision (CVNormalization by an internal reference improved interscanner ADC reproducibility. High-resolution protocols yielded comparably accurate and significantly less variable ADCs compared to a clinical standard protocol.2 TECHNICAL EFFICACY: Stage 1.

Background Diffusion magnetic resonance imaging (MRI) is integral to detection of prostate cancer (PCa), but conventional apparent diffusion coefficient (ADC) cannot capture the complexity of prostate tissues and tends to yield noisy images that do not distinctly highlight cancer. A four-compartment restriction spectrum imaging (RSI4 ) model was recently found to optimally characterize pelvic diffusion signals, and the model coefficient for the slowest diffusion compartment, RSI4 -C1 , yielded greatest tumor conspicuity. Purpose To evaluate the slowest diffusion compartment of a four-compartment spectrum imaging model (RSI4 -C1 ) as a quantitative voxel-level classifier of PCa. Study type Retrospective. Subjects Forty-six men who underwent an extended MRI acquisition protocol for suspected PCa. Twenty-three men had benign prostates, and the other 23 men had PCa. Field strength/sequence A 3 T, multishell diffusion-weighted and axial T2-weighted sequences. Assessment High-confidence cancer voxels were delineated by expert consensus, using imaging data and biopsy results. The entire prostate was considered benign in patients with no detectable cancer. Diffusion images were used to calculate RSI4 -C1 and conventional ADC. Classifier images were also generated. Statistical tests Voxel-level discrimination of PCa from benign prostate tissue was assessed via receiver operating characteristic (ROC) curves generated by bootstrapping with patient-level case resampling. RSI4 -C1 was compared to conventional ADC for two metrics: area under the ROC curve (AUC) and false-positive rate for a sensitivity of 90% (FPR90 ). Statistical significance was assessed using bootstrap difference with two-sided α = 0.05. Results RSI4 -C1 outperformed conventional ADC, with greater AUC (mean 0.977 [95% CI: 0.951-0.991] vs. 0.922 [0.878-0.948]) and lower FPR90 (0.032 [0.009-0.082] vs. 0.201 [0.132-0.290]). These improvements were statistically significant (P Data conclusion RSI4 -C1 yielded a quantitative, voxel-level classifier of PCa that was superior to conventional ADC. RSI classifier images with a low false-positive rate might improve PCa detection and facilitate clinical applications like targeted biopsy and treatment planning. Evidence level 3 TECHNICAL EFFICACY: Stage 2.

Background Diffusion-weighted (DW) echo-planar imaging (EPI) is prone to geometric distortions due to B0 inhomogeneities. Both prospective and retrospective approaches have been developed to decrease and correct such distortions. Purpose The purpose of this work was to evaluate the performance of reduced-field-of-view (FOV) acquisition and retrospective distortion correction methods in decreasing distortion artifacts for breast imaging. Coverage of the axilla in reduced-FOV DW magnetic resonance imaging (MRI) and residual distortion were also assessed. Study type Retrospective. Population/phantom Breast phantom and 169 women (52.4 ± 13.4 years old) undergoing clinical breast MRI. Field strength/sequence A 3.0 T/ full- and reduced-FOV DW gradient-echo EPI sequence. Assessment Performance of reversed polarity gradient (RPG) and FSL topup in correcting breast full- and reduced-FOV EPI data was evaluated using the mutual information (MI) metric between EPI and anatomical images. Two independent breast radiologists determined if coverage on both EPI data sets was adequate to evaluate axillary nodes and identified residual nipple distortion artifacts. Statistical tests Two-way repeated-measures analyses of variance and post hoc tests were used to identify differences between EPI modality and distortion correction method. Generalized linear mixed effects models were used to evaluate differences in axillary coverage and residual nipple distortion. Results In a breast phantom, residual distortions were 0.16 ± 0.07 cm and 0.22 ± 0.13 cm in reduced- and full-FOV EPI with both methods, respectively. In patients, MI significantly increased after distortion correction of full-FOV (11 ± 5% and 18 ± 9%, RPG and topup) and reduced-FOV (8 ± 4% both) EPI data. Axillary nodes were observed in 99% and 69% of the cases in full- and reduced-FOV EPI images. Residual distortion was observed in 93% and 0% of the cases in full- and reduced-FOV images. Data conclusion Minimal distortion was achieved with RPG applied to reduced-FOV EPI data. RPG improved distortions for full-FOV images but with more modest improvements and limited correction near the nipple. Evidence level 3 TECHNICAL EFFICACY: Stage 1.

Purpose: Diffusion-weighted MRI (DW-MRI) is a contrast-free modality that has demonstrated ability to discriminate between predefined benign and malignant breast lesions. However, how well DW-MRI discriminates cancer from all other breast tissue voxels in a clinical setting is unknown. Here we explore the voxelwise ability to distinguish cancer from healthy breast tissue using signal contributions from the newly developed three-component multi-b-value DW-MRI model. Experimental Design: Patients with pathology-proven breast cancer from two datasets (n = 81 and n = 25) underwent multi-b-value DW-MRI. The three-component signal contributions C1 and C2 and their product, C1C2, and signal fractions F1, F2, and F1F2 were compared with the image defined on maximum b-value (DWImax), conventional apparent diffusion coefficient (ADC), and apparent diffusion kurtosis (Kapp). The ability to discriminate between cancer and healthy breast tissue was assessed by the false-positive rate given a sensitivity of 80% (FPR80) and ROC AUC. Results: Mean FPR80 for both datasets was 0.016 [95% confidence interval (CI), 0.008–0.024] for C1C2, 0.136 (95% CI, 0.092–0.180) for C1, 0.068 (95% CI, 0.049–0.087) for C2, 0.462 (95% CI, 0.425–0.499) for F1F2, 0.832 (95% CI, 0.797–0.868) for F1, 0.176 (95% CI, 0.150–0.203) for F2, 0.159 (95% CI, 0.114–0.204) for DWImax, 0.731 (95% CI, 0.692–0.770) for ADC, and 0.684 (95% CI, 0.660–0.709) for Kapp. Mean ROC AUC for C1C2 was 0.984 (95% CI, 0.977–0.991). Conclusions: The C1C2 parameter of the three-component model yields a clinically useful discrimination between cancer and healthy breast tissue, superior to other DW-MRI methods and obliviating predefining lesions. This novel DW-MRI method may serve as noncontrast alternative to standard-of-care dynamic contrast-enhanced MRI.

BACKGROUND Multicompartmental modeling outperforms conventional diffusion-weighted imaging (DWI) in the assessment of prostate cancer. Optimized multicompartmental models could further improve the detection and characterization of prostate cancer. PURPOSE To optimize multicompartmental signal models and apply them to study diffusion in normal and cancerous prostate tissue in vivo. STUDY TYPE Retrospective. SUBJECTS Forty-six patients who underwent MRI examination for suspected prostate cancer; 23 had prostate cancer and 23 had no detectable cancer. FIELD STRENGTH/SEQUENCE 3T multishell diffusion-weighted sequence. ASSESSMENT Multicompartmental models with 2-5 tissue compartments were fit to DWI data from the prostate to determine optimal compartmental apparent diffusion coefficients (ADCs). These ADCs were used to compute signal contributions from the different compartments. The Bayesian Information Criterion (BIC) and model-fitting residuals were calculated to quantify model complexity and goodness-of-fit. Tumor contrast-to-noise ratio (CNR) and tumor-to-background signal intensity ratio (SIR) were computed for conventional DWI and multicompartmental signal-contribution maps. STATISTICAL TESTS Analysis of variance (ANOVA) and two-sample t-tests (α = 0.05) were used to compare fitting residuals between prostate regions and between multicompartmental models. T-tests (α = 0.05) were also used to assess differences in compartmental signal-fraction between tissue types and CNR/SIR between conventional DWI and multicompartmental models. RESULTS The lowest BIC was observed from the 4-compartment model, with optimal ADCs of 5.2e-4, 1.9e-3, 3.0e-3, and >3.0e-2 mm2 /sec. Fitting residuals from multicompartmental models were significantly lower than from conventional ADC mapping (P

Magnetic resonance imaging (MRI) is used for preoperative evaluation, high-risk screening, and other select indications for breast cancer. However, the interpretation of breast MR images in pregnant and lactating women is complicated by physiologic changes of the breast that may result in marked background enhancement. Breast MRI with contrast administration is contraindicated in pregnancy. Restriction spectrum imaging (RSI) is an advanced diffusion-weighted (DW)-MRI method that theoretically reflects signal from cells with high nuclear-to-cytoplasm ratio without gadolinium-based contrast. This report describes a case in which RSI notably increased tumor conspicuity in a lactating woman, compared to contrast-enhanced (CE)-MRI and conventional DW-MRI.

One promising approach for mapping CMRO2 is dual-calibrated functional MRI (dc-fMRI). This method exploits the Fick Principle to combine estimates of CBF from ASL, and OEF derived from BOLD-ASL measurements during arterial O2 and CO2 modulations. Multiple gas modulations are required to decouple OEF and deoxyhemoglobin-sensitive blood volume. We propose an alternative single gas calibrated fMRI framework, integrating a model of oxygen transport, that links blood volume and CBF to OEF and creates a mapping between the maximum BOLD signal, CBF and OEF (and CMRO2). Simulations demonstrated the method’s viability within physiological ranges of mitochondrial oxygen pressure, PmO2, and mean capillary transit time. A dc-fMRI experiment, performed on 20 healthy subjects using O2 and CO2 challenges, was used to validate the approach. The validation conveyed expected estimates of model parameters (e.g., low PmO2), with spatially uniform OEF maps (grey matter, GM, OEF spatial standard deviation ≈ 0.13). GM OEF estimates obtained with hypercapnia calibrated fMRI correlated with dc-fMRI (r = 0.65, p = 2·10−3). For 12 subjects, OEF measured with dc-fMRI and the single gas calibration method were correlated with whole-brain OEF derived from phase measures in the superior sagittal sinus (r = 0.58, p = 0.048; r = 0.64, p = 0.025 respectively). Simplified calibrated fMRI using hypercapnia holds promise for clinical application.

Patients with obstructive sleep apnea (OSA) are at elevated risk of developing systemic vascular disease and cognitive dysfunction. Here, cerebral oxygen metabolism was assessed in patients with OSA by means of a magnetic resonance-based method involving simultaneous measurements of cerebral blood flow rate and venous oxygen saturation in the superior sagittal sinus for a period of 10 minutes at an effective temporal resolution of 1.3 seconds before, during, and after repeated 24-second breath-holds mimicking spontaneous apneas, yielding, along with pulse oximetry-derived arterial saturation, whole-brain CMRO2 via Fick’s Principle. Enrolled subjects were classified based on their apnea-hypopnea indices into OSA (N = 31) and non-sleep apnea reference subjects (NSA = 21), and further compared with young healthy subjects (YH, N = 10). OSA and NSA subjects were matched for age and body mass index. CMRO2 was lower in OSA than in the YH group during normal breathing (105.6 ± 14.1 versus 123.7 ± 22.8 μmol O2/min/100g, P = 0.01). Further, the fractional change in CMRO2 in response to a breath-hold challenge was larger in OSA than in the YH group (15.2 ± 9.2 versus 8.5 ± 3.4%, P = 0.04). However, there was no significant difference in CMRO2 between OSA and NSA subjects. The data suggest altered brain oxygen metabolism in OSA and possibly in NSA as well.

Diffusion-weighted MRI (DW-MRI) offers a potential adjunct to dynamic contrast-enhanced MRI to discriminate benign from malignant breast lesions by yielding quantitative information about tissue microstructure. Multi-component modeling of the DW-MRI signal over an extended b-value range (up to 3000 s/mm2) theoretically isolates the slowly diffusing (restricted) water component in tissues. Previously, a three-component restriction spectrum imaging (RSI) model demonstrated the ability to distinguish malignant lesions from healthy breast tissue. We further evaluated the utility of this three-component model to differentiate malignant from benign lesions and healthy tissue in 12 patients with known malignancy and synchronous pathology-proven benign lesions. The signal contributions from three distinct diffusion compartments were measured to generate parametric maps corresponding to diffusivity on a voxel-wise basis. The three-component model discriminated malignant from benign and healthy tissue, particularly using the restricted diffusion C1 compartment and product of the restricted and intermediate diffusion compartments (C1 and C2). However, benign lesions and healthy tissue did not significantly differ in diffusion characteristics. Quantitative discrimination of these three tissue types (malignant, benign, and healthy) in non-pre-defined lesions may enhance the clinical utility of DW-MRI in reducing excessive biopsies and aiding in surveillance and surgical evaluation without repeated exposure to gadolinium contrast.

PURPOSE: Restriction spectrum imaging (RSI) decomposes the diffusion-weighted (DW) MRI signal into separate diffusion components of known apparent diffusion coefficients (ADCs). The number of diffusion components and optimal ADCs for RSI are organ-specific and determined empirically. The purpose of this work was to determine the RSI model for breast tissues. METHODS: The DW-MRI signal was described using a linear combination of multiple exponential components. A set of ADC values was estimated to fit voxel in cancer and control regions of interest (ROIs). Later, the signal contributions of each diffusion component were estimated using these fixed ADC values. Relative fitting residual and Bayesian information criterion (BIC) were assessed. Contrast-to-noise ratio (CNR) between cancer and fibroglandular tissue in RSI-derived signal contribution maps was compared to dynamic contrast enhanced (DCE) imaging. RESULTS: A total of 74 women with breast cancer were scanned at 3.0T MRI. The fitting residuals of conventional ADC and BIC suggest that a three-component model improves the characterization of the diffusion signal over a bi-exponential model. Estimated ADCs of tri-exponential model were D(1,3)=0, D(2,3)=1.5×10(−3) and D(3,3)=10.8×10(−3) mm(2)/s. The RSI-derived signal contributions of the slower diffusion components were larger in tumors than in fibroglandular tissues. Further, the CNR and specificity at 80% sensitivity of DCE and a subset of RSI-derived maps were equivalent. CONCLUSION: Breast DW-MRI signal was best described using a tri-exponential model. Tumor conspicuity in breast RSI model is comparable to that of DCE without the use of exogenous contrast. These data may be used as differential features between healthy and malignant breast tissues.

Functional MRI (fMRI) can identify active foci in response to stimuli through BOLD signal fluctuations, which represent a complex interplay between blood flow and cerebral metabolic rate of oxygen (CMRO2) changes. Calibrated fMRI can disentangle the underlying contributions, allowing quantification of the CMRO2 response. Here, whole-brain venous oxygen saturation ( Y v) was computed alongside ASL-measured CBF and BOLD-weighted data to derive the calibration constant, M, using the proposed Y v-based calibration. Data were collected from 10 subjects at 3T with a three-part interleaved sequence comprising background-suppressed 3D-pCASL, 2D BOLD-weighted, and single-slice dual-echo GRE (to measure Y v via susceptometry-based oximetry) acquisitions while subjects breathed normocapnic/normoxic, hyperoxic, and hypercapnic gases, and during a motor task. M was computed via Y v-based calibration from both hypercapnia and hyperoxia stimulus data, and results were compared to conventional hypercapnia or hyperoxia calibration methods. Mean M in gray matter did not significantly differ between calibration methods, ranging from 8.5 ± 2.8% (conventional hyperoxia calibration) to 11.7 ± 4.5% (Yv-based calibration in response to hyperoxia), with hypercapnia-based M values between ( p = 0.56). Relative CMRO2 changes from finger tapping were computed from each M map. CMRO2 increased by ∼20% in the motor cortex, and good agreement was observed between the conventional and proposed calibration methods.

PurposeMultiparametric MRI (mpMRI) improves detection of clinically significant prostate cancer (csPCa), but the qualitative PI-RADS system and quantitative apparent diffusion coefficient (ADC) yield inconsistent results. An advanced Restrictrion Spectrum Imaging (RSI) model may yield a better quantitative marker for csPCa, the RSI restriction score (RSIrs). We evaluated RSIrs for patient-level detection of csPCa.Materials and MethodsRetrospective analysis of men who underwent mpMRI with RSI and prostate biopsy for suspected prostate cancer from 2017-2019. Maximum RSIrs within the prostate was assessed by area under the receiver operating characteristic curve (AUC) for discriminating csPCa (grade group ≥2) from benign or grade group 1 biopsies. Performance of RSIrs was compared to minimum ADC and PI-RADS v2-2.1via bootstrap confidence intervals and bootstrap difference (two-tailed α=0.05). We also tested whether the combination of PI-RADS and RSIrs (PI-RADS+RSIrs) was superior to PI-RADS, alone.Results151 patients met criteria for inclusion. AUC values for ADC, RSIrs, and PI-RADS were 0.50 [95% confidence interval: 0.41, 0.60], 0.76 [0.68, 0.84], and 0.78 [0.71, 0.85], respectively. RSIrs (p=0.0002) and PI-RADS (prs was comparable to that of PI-RADS (p=0.6). AUC for PI-RADS+RSIrs was 0.84 [0.77, 0.90], superior to PI-RADS or RSIrs, alone (p=0.008, p=0.009).ConclusionsRSIrs was superior to conventional ADC and comparable to (routine, clinical) PI-RADS for patient-level detection of csPCa. The combination of PI-RADS and RSIrs was superior to either alone. RSIrs is a promising quantitative marker worthy of prospective study in the setting of csPCa detection.DisclosuresMEH reports honoraria from Multimodal Imaging Services Corporation and research funding from General Electric Healthcare. AMD is a Founder of and holds equity in CorTechs Labs, Inc, and serves on its Scientific Advisory Board. He is a member of the Scientific Advisory Board of Human Longevity, Inc. and receives funding through research agreements with General Electric Healthcare. The terms of these arrangements have been reviewed and approved by the University of California San Diego in accordance with its conflict-of-interest policies. TMS reports honoraria from Multimodal Imaging Services Corporation, Varian Medical Systems, and WebMD; he has an equity interest in CorTechs Labs, Inc. and also serves on its Scientific Advisory Board. These companies might potentially benefit from the research results. The terms of this arrangement have been reviewed and approved by the University of California San Diego in accordance with its conflict-of-interest policies.

Diffusion-weighted (DW) echo-planar imaging (EPI) is prone to geometric distortions due to BThe purpose of this work was to evaluate the performance of reduced-field-of-view (FOV) acquisition and retrospective distortion correction methods in decreasing distortion artifacts for breast imaging. Coverage of the axilla in reduced-FOV DW magnetic resonance imaging (MRI) and residual distortion were also assessed.Retrospective.Breast phantom and 169 women (52.4 ± 13.4 years old) undergoing clinical breast MRI.A 3.0 T/ full- and reduced-FOV DW gradient-echo EPI sequence.Performance of reversed polarity gradient (RPG) and FSL topup in correcting breast full- and reduced-FOV EPI data was evaluated using the mutual information (MI) metric between EPI and anatomical images. Two independent breast radiologists determined if coverage on both EPI data sets was adequate to evaluate axillary nodes and identified residual nipple distortion artifacts.Two-way repeated-measures analyses of variance and post hoc tests were used to identify differences between EPI modality and distortion correction method. Generalized linear mixed effects models were used to evaluate differences in axillary coverage and residual nipple distortion.In a breast phantom, residual distortions were 0.16 ± 0.07 cm and 0.22 ± 0.13 cm in reduced- and full-FOV EPI with both methods, respectively. In patients, MI significantly increased after distortion correction of full-FOV (11 ± 5% and 18 ± 9%, RPG and topup) and reduced-FOV (8 ± 4% both) EPI data. Axillary nodes were observed in 99% and 69% of the cases in full- and reduced-FOV EPI images. Residual distortion was observed in 93% and 0% of the cases in full- and reduced-FOV images.Minimal distortion was achieved with RPG applied to reduced-FOV EPI data. RPG improved distortions for full-FOV images but with more modest improvements and limited correction near the nipple.3 TECHNICAL EFFICACY: Stage 1.

PurposeDiffusion-weighted magnetic resonance imaging (DW-MRI) is a contrast-free modality that has demonstrated ability to discriminate between pre-defined benign and malignant breast lesions. However, the ability of DW-MRI to discriminate cancer tissue from all other breast tissues in a clinical setting is unknown. Here we explore the ability to distinguish breast cancer from healthy breast tissues using signal contributions from the newly developed three-component multi-b-value DW-MRI model.Experimental designPathology-proven breast cancer patients from two datasets (n=81 and n=25) underwent multi-b-value DW-MRI. The three-component signal contributions C1 and C2 and their product, C1C2, were compared to the image defined on maximum b-value (DWImax), conventional apparent diffusion coefficient (ADC), and apparent diffusion kurtosis (Kapp). Ability to discriminate between cancer and healthy breast tissues was assessed by the false positive rate given sensitivity of 80% (FPR80) and receiver operating characteristic (ROC) area under the curve (AUC).ResultsMean FPR80 for both datasets was 0.016 (95%CI=0.008–0.024) for C1C2, 0.136 (95%CI=0.092–0.180) for C1, 0.068 (95%CI=0.049–0.087) for C2, 0.159 (95%CI=0.114–0.204) for DWImax, 0.731 (95%CI=0.692–0.770) for ADC and 0.684 (95%CI=0.660–0.709) for Kapp. Mean ROC AUC for C1C2 was 0.984 (95%CI=0.977–0.991).ConclusionsThe three-component model yields a clinically useful discrimination between cancer and healthy breast tissues, superior to other DW-MRI methods and obliviating pre-defining lesions by radiologists. This novel DW-MRI method may serve as non-contrast alternative to standard-of-care dynamic contrast-enhanced MRI (DCE-MRI); removing the need to administer Gadolinium contrast decreases scan time and any accumulation of Gadolinium in the brain.

PurposeDiffusion MRI is integral to detection of prostate cancer (PCa), but conventional ADC cannot capture the complexity of prostate tissues. A four-compartment restriction spectrum imaging (RSI4) model was recently found to optimally characterize pelvic diffusion signals, and the model coefficient for the slowest diffusion compartment, RSI4-C1, yielded greatest tumor conspicuity. In this study, RSI4-C1 was evaluated as a quantitative voxel-level classifier of PCa.MethodsThis was a retrospective analysis of 46 men who underwent an expanded-acquisition pelvic MRI for suspected PCa. Twenty-three men had no detectable cancer on biopsy or clinical follow-up; the other 23 had biopsy-proven PCa corresponding to a lesion on MRI (PI-RADS category 3-5). High-confidence cancer voxels were delineated by expert consensus, using imaging data and biopsy results. The entire prostate was considered benign in patients with no detectable cancer. Diffusion images were used to calculate RSI4-C1 and conventional ADC. Voxel-level discrimination of PCa from benign prostate tissue was assessed via receiver operating characteristic (ROC) curves generated by bootstrapping with patient-level case resampling. Specifically, we compared RSI4-C1 and conventional ADC on mean (and 95% CI) for two metrics: area under the curve (AUC) and false-positive rate for a sensitivity of 90% (FPR90). Classifier images were also compared.ResultsRSI4-C1 outperformed conventional ADC, with greater AUC [0.977 (0.951-0.991) vs. 0.921 (0.873-0.949)] and lower FPR90 [0.033 (0.009-0.083) vs. 0.201 (0.131-0.300)].ConclusionRSI4-C1 yielded a quantitative, voxel-level classifier of PCa that was superior to conventional ADC. RSI classifier images with a low false-positive rate might improve PCa detection.

PurposeDiffusion weighted (DW) echo-planar imaging (EPI) is prone to geometric and intensity distortions due to B0 inhomogeneities. Pulse sequences that excite spins within a reduced field-of-view (FOV) in the phase encoding (PE) direction have been developed to decrease such distortions. In addition, use of the reverse polarity gradient (RPG) method, a retrospective approach to correct distortion artifacts, has been shown to improve the localization of tumor lesions. The purpose of this work was to evaluate the performance of reduced-FOV acquisition and RPG in decreasing distortion artifacts for breast imaging.MethodsEPI data were acquired with full and reduced-FOV in a breast phantom and in a group of 170 women at 3T. The performance of RPG in correcting distortion artifacts in EPI data was evaluated using the mutual information (MI) metric between EPI and anatomical low-distortion images before and after distortion correction.ResultsRPG corrected distortions by 61% in full-FOV EPI and 48% in reduced-FOV EPI in a breast phantom. In patients, MI increased on average 13±8% and 8±6% for both full and reduced-FOV EPI data after distortion correction, respectively. The 95th percentile and maximum displacement between uncorrected and corrected full-FOV EPI datasets were 0.8±0.3cm and 1.9±0.3cm, and for reduced-FOV were 0.4±0.2cm and 1.3±0.3cm.ConclusionMinimal distortion was achieved with RPG applied to reduced-FOV EPI data. RPG improved distortions for full-FOV, but with more modest improvements and limited correction near the nipple.

BackgroundOptimizing a restriction spectrum imaging (RSI) model for the prostate could lead to improved characterization of diffusion in the prostate and better discrimination of tumors.PurposeTo determine optimal apparent diffusion coefficients (ADCs) for prostate RSI models and evaluate the number of tissue compartments required to best describe diffusion in prostate tissue.Study TypeRetrospective.Population/SubjectsForty-six patients who underwent an extended MRI examination for suspected prostate cancer; 23 had prostate tumors and 23 had no detectable cancer.Field strength/Sequence3T multi-shell diffusion weighted sequence.AssessmentRSI models with 2-5 tissue compartments were fit to multi-shell DWI data from the prostate to determine optimal compartmental ADCs. Signal contributions from the different tissue compartments were computed using these ADCs and compared between normal tissues (peripheral zone, transition zone, seminal vesicles) and tumors.Statistical TestsThe Bayesian Information Criterion (BIC) was used to evaluate the optimality of different RSI models. Model-fitting residual (as percent variance) was recorded to assess the models’ goodness-of-fit and whether it varied between anatomical regions of the prostate. Two-sample t-tests (α=0.05) were used to determine the statistical significance of any differences observed in compartmental signal-fraction between normal prostate tissue and tumors.ResultsThe lowest BIC was observed from the 4-compartment model. Optimal ADCs for the 4 compartments were 5.2e-4, 1.9e-3, 3.0e-3, and ≫3.0e-3 mm2/s. Tumor tissue showed the largest reduction in fitting residual by increasing model order. Prostate tumors had a significantly (P≪0.05) greater proportion of signal from compartments 1 and 2 than normal tissue. Tumor conspicuity in compartment 1 increased substantially with model order.Data ConclusionAmong the examined RSI models, the 4-compartment model best described the diffusion-signal characteristics of the prostate. Compartmental signal fractions revealed by such a model may improve discrimination between cancerous and benign prostate tissue.

Magnetic resonance imaging (MRI) is a diagnostic tool that can be used to noninvasively assess lumbar muscle size and fatty infiltration, important biomarkers of muscle health. Diffusion tensor imaging (DTI) is an MRI technique that is sensitive to muscle microstructural features such as fiber size (an important biomarker of muscle health), which is typically only assessed using invasive biopsy techniques. The goal of this study was to establish normative values of level‐dependent lumbar muscle size, fat signal fraction, and restricted diffusion assessed by MRI in a highly active population. Forty‐two active‐duty Marines were imaged using a (a) high‐resolution anatomical, (b) fat‐water separation, and (c) DT‐MRI scan. The multifidus and erector spinae muscles were compared at each level using two‐way repeated measures ANOVA. Secondary analysis included Three dimensional (3D) reconstructions to qualitatively assess lumbar muscle size, fatty infiltration, and fiber orientation via tractography. The erector spinae was found to be larger than the multifidus above L5, with lower fat signal fraction above L3, and a less restricted diffusion profile than the multifidus above L4, with this pattern reversed in the lower lumbar spine. 3D reconstructions demonstrated accumulations of epimuscular fat in the anterior and posterior regions of the lumbar musculature, with minimal intramuscular fatty infiltration. Tractography images demonstrated different orientations of adjacent lumbar musculature, which cannot be visualized with standard MRI pulse sequences. The level dependent differences found in this study provide a normative baseline, for which to better understand whole muscle and microstructural changes associated with aging, low back pain, and pathology., Magnetic resonance imaging (MRI) is a diagnostic tool that can be used to noninvasively assess lumbar muscle size and fatty infiltration, important biomarkers of muscle health. Diffusion tensor imaging (DTI) is an MRI technique that is sensitive to muscle microstructural features such as fiber size (an important biomarker of muscle health), which is typically only assessed using invasive biopsy techniques. The goal of this study was to establish normative values of level‐dependent lumbar muscle size, fat signal fraction, and restricted diffusion assessed by MRI in a highly active population.

Purpose The purpose of this study was to estimate fetal O2 delivery rate in vivo across a range of gestational ages (GA). Toward this, a calibration equation for T2-based oximetry was derived. Methods Umbilical cord blood of varying hematocrit (Hct) and oxygen saturation (HbO2) levels was prepared and T2 measured using a T2-prepared balanced steady-state free precession (T2-bSSFP) sequence at 1.5T. The relationship between blood R2=1/T2, HbO2 and Hct was established based on the model R2 = (1 − Hct)R2,plasma + Hct R2,RBC + k · Hct · (1 − Hct) · (1 − HbO2)2. Experimental R2, HbO2 and Hct levels were fit to the model yielding values of k, R2,plasma and R2,RBC (R2 of plasma and erythrocytes). Umbilical vein (UV) T2 measured in vivo was then converted to HbO2 yielding, together with blood flow rate (BFR), fetal O2 delivery rate in 22 pregnancies (GA 30±3 weeks). Results Constants derived from the fit (R2 = 0.94) were: k=83.1s−1, R2,plasma = 1.1s−1, R2,RBC = 12.9s−1. R2,RBC and k were found to be larger than those obtained for adult blood, likely due to differences in dominant hemoglobin type. Data suggest that the use of adult blood calibration could entail errors up 10% in fetal blood HbO2. Average UV BFR (89.5±17.2 mL/min/kg), HbO2 (84±7%,) and fetal O2 delivery rate (15.1±3.8 mL O2/min/kg) were independent of GA. Fetal O2 delivery rate agreed well with results obtained with invasive methods at term. Conclusion The present work describes strategies for measuring UV BFR and HbO2 in vivo and estimates fetal O2 delivery rate noninvasively with quantitative MRI during the second and third trimesters of pregnancy.

PURPOSE:To investigate the feasibility of estimating calibration constants (K and T2o ) in vivo for converting whole-blood T2 to blood hemoglobin oxygen saturation (HbO2 ) according to the Luz-Meiboom model, 1/T2=1/T2o+K(1-HbO2)2, where K and T2o are relaxivity and transverse relaxation time of fully saturated blood, respectively. METHODS:A range of HbO2 values was achieved in the superficial femoral vein with intermittent cuff occlusion in seven healthy adults (four males) to establish a calibration curve between blood T2 and HbO2 at 1.5T. HbO2 was derived via MR susceptometry, a technique previously validated, and the transverse relaxation time was quantified with an optimized T2 -prepared balanced steady-state free precession pulse sequence. To evaluate the accuracy of the in vivo calibration method, T2 and HbO2 were quantified in the superior sagittal sinus in six additional subjects and compared with susceptometry. RESULTS:Two sets of gender-specific calibration constants were derived, one for each gender corresponding to hematocrits of 0.47 ± 0.02 for males and 0.38 ± 0.01 for females, yielding K/T2o = 41 Hz/260 ms and 26 Hz/280 ms, respectively. The in vivo calibration returned physiologically plausible superior sagittal sinus SvO2 values (65 ± 5% HbO2 ), and there was no significant difference between the results from the two methods (average difference -0.3% HbO2 ). CONCLUSION:The results show feasibility of performing in vivo calibration for converting whole-blood T2 to HbO2 . The proposed approach bypasses the involved and cumbersome processes associated with in vitro calibration. Magn Reson Med 79:2290-2296, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Author(s): Rodriguez-Soto, Ana E; Berry, David B; Palombo, Laura; Valaik, Emily; Kelly, Karen R; Ward, Samuel R | Abstract: Study designRepeated measures.ObjectiveThe purpose of this study was to quantify the effect of operationally relevant loads and distributions on lumbar spine (LS) in a group of active-duty Marines.Summary of background dataLow-back pain has been associated with heavy load carriage among military personnel. Although there are data describing the LS posture in response to load, the effect of varying load characteristics on LS posture remains unknown.MethodsMagnetic resonance images of Marines (n = 12) were acquired when standing unloaded and when carrying 22, 33, and 45 kg of load distributed both 50% to 50% and 20% to 80% anteriorly and posteriorly. Images were used to measure LS and pelvic postures. Two-way repeated-measures ANOVA and posthoc tests were used to compare LS posture across load magnitudes and distributions (α = 0.05). This project was founded by the US Army Medical Research Acquisition Activity, Award No. W81XWH-13-2-0043, under Work Unit No. 1310.ResultsNo changes in LS posture were induced when load was evenly distributed. When load was carried in the 20% to 80% distribution lumbosacral flexion increased as a result of sacral anterior rotation and overall reduced lumbar lordosis. This pattern was greater as load was increased between 22 and 33 kg, but did not increase further between 33 and 45 kg. We observed that the inferior LS became uniformly less lordotic, independently of load magnitude. However, the superior LS became progressively more lordotic with increasing load magnitude CONCLUSION.: Postural adaptations were found only when load was carried with a posterior bias, suggesting that load-carriage limits based on postural changes are relevant when loads are nonuniformly distributed. Although the tendency would be to interpret that loads should be carried symmetrically to protect the spine, the relationship between postural changes and injury are not clear. Finally, the operational efficiency of carrying load in this distribution needs to be tested.Level of evidence3.

© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. Low back pain has a 70% higher prevalence in members of the armed forces than in the general population, possibly due to the loads and positions soldiers experience during training and combat. Although the influence of heavy load carriage on standing lumbar spine posture in this population is known, postures in other operationally relevant positions are unknown. Therefore, the purpose of this study was to characterize the effect of simulated military operational positions under relevant loading conditions on global and local lumbar spine postures in active duty male US Marines. Secondary objectives were to evaluate if intervertebral disc degeneration and low back pain affect lumbar spine postures. Magnetic resonance images were acquired on an upright scanner in the following operational positions: Natural standing with no external load, standing with body armor (11.3 kg), sitting with body armor, and prone on elbows with body armor. Custom software was used to measure global lumbar spine posture: Lumbosacral flexion, sacral slope, lordosis, local measures of intervertebral angles, and intervertebral distances. Sitting resulted in decreased lumbar lordosis at all levels of the spine except L1–L2. When subjects were prone on elbows, a significant increase in local lordosis was observed only at L5–S1 compared with all other positions. Marines with disc degeneration (77%) or history of low back pain (72%) had decreased lumbar range of motion and less lumbar extension than healthy Marines. These results indicate that a male Marine's pathology undergoes a stereotypic set of postural changes during functional tasks, which may impair performance. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2145–2153, 2017.

Obstructive sleep apnea (OSA) is characterized by intermittent obstruction of the airways during sleep. Cerebrovascular reactivity (CVR) is an index of cerebral vessels' ability to respond to a vasoactive stimulus, such as increased CO2. We hypothesized that OSA alters CVR, expressed as a breath-hold index (BHI) defined as the rate of change in CBF or BOLD signal during a controlled breath-hold stimulus mimicking spontaneous apneas by being both hypercapnic and hypoxic. In 37 OSA and 23 matched non sleep apnea (NSA) subjects, we obtained high temporal resolution CBF and BOLD MRI data before, during, and between five consecutive BH stimuli of 24 s, each averaged to yield a single BHI value. Greater BHI was observed in OSA relative to NSA as derived from whole-brain CBF (78.6 ± 29.6 vs. 60.0 ± 20.0 mL/min2/100 g, P = 0.010) as well as from flow velocity in the superior sagittal sinus (0.48 ± 0.18 vs. 0.36 ± 0.10 cm/s2, P = 0.014). Similarly, BOLD-based BHI was greater in OSA in whole brain (0.19 ± 0.08 vs. 0.15 ± 0.03%/s, P = 0.009), gray matter (0.22 ± 0.09 vs. 0.17 ± 0.03%/s, P = 0.011), and white matter (0.14 ± 0.06 vs. 0.10 ± 0.02%/s, P = 0.010). The greater CVR is not currently understood but may represent a compensatory mechanism of the brain to maintain oxygen supply during intermittent apneas.

Background The relationship between lumbar spine posture and muscle structure is not well understood. Objectives To investigate the predictive capacity of muscle structure on lumbar spine posture in active-duty Marines. Methods Forty-three Marines were scanned in this cross-sectional study, using an upright magnetic resonance imaging scanner while standing without load and standing, sitting, and prone on elbows with body armor. Cobb, horizontal, and sacral angles were measured. Marines were then scanned while unloaded in supine using a supine magnetic resonance imaging scanner. The imaging protocol consisted of T2 intervertebral disc mapping; high-resolution, anatomical, fat-water separation, and diffusion tensor imaging to quantify disc hydration and muscle volume, fat fraction, and restricted diffusion profiles in the lumbar muscles. A stepwise multiple linear regression model was used to identify physiological measures predictive of lumbar spine posture. Results The multiple regression model demonstrated that fractional anisotropy of the erector spinae was a significant predictor of lumbar posture for 7 of 18 dependent variables measured, and explained 20% to 35% of the variance in each model. Decreased fractional anisotropy of the erector spinae predicted decreased lordosis, lumbosacral extension, and anterior pelvic tilt. Conclusion Fractional anisotropy is inversely related with muscle fiber size, which is associated with the isometric force-generating capacity of a muscle fiber. This suggests that stronger erector spinae muscles predict decreased lordosis, lumbosacral extension, and anterior pelvic tilt in a highly trained population. J Orthop Sports Phys Ther 2018;48(8):613-621. Epub 17 May 2018. doi:10.2519/jospt.2018.7865.

© 2015 Human Kinetics, Inc. Vertebral level-dependent, angular, and linear translations of the spine have been measured in 2D and 3D using several imaging methods to quantify postural changes due to loading conditions and tasks. Here, we propose and validate a semiautomated method for measuring lumbar intervertebral angles and translations from upright MRI images using an endplate-based, joint coordinate system (JCS). This method was validated using 3D printed structures, representing intervertebral discs (IVD) at predetermined angles and heights, which were positioned between adjacent cadaveric vertebrae as a gold standard. Excellent agreement between our measurements and the gold standard was found for intervertebral angles in all anatomical planes (ICC >.997) and intervertebral distance measurements (ICC >.949). The proposed endplate-based JCS was compared with the vertebral body-based JCS proposed by the International Society of Biomechanics (ISB) using the 3D printed structures placed between 3 adjacent vertebrae from a cadaver with scoliosis. The endplate-based method was found to have better agreement with angles in the sagittal plane (ICC = 0.985) compared with the vertebral body-based method (ICC =.280). Thus, this method is accurate for measuring 3D intervertebral angles in the healthy and diseased lumbar spine.

PURPOSE To establish a calibration equation to convert human blood T2 to the full range of oxygen saturation levels (HbO2 ) and physiologic hematocrit (Hct) values using a T2 -prepared balanced steady-state free precession sequence (T2 -SSFP) at 1.5T. METHODS Blood drawn from 10 healthy donors (29.1 ± 3.9 years old) was prepared into samples of varying HbO2 and Hct (n = 79), and imaged using T2 -SSFP sequence at 37°C and interrefocusing interval τ180 = 12 ms. The relationship between blood T2 , HbO2 , and Hct was established based on the model R2=R2,plasma+Hct (R2,RBC-R2,plasma)+k·Hct·(1-Hct)·(1-HbO2)2. Measured R2 and HbO2 levels were fit by the model yielding values of R2,plasma, R2,RBC, and k. T2 -SSFP and the established calibration equation were applied to extract HbO2 at the superior sagittal sinus (SSS) in vivo and were compared with susceptometry-based oximetry. RESULTS Constants derived from the fit were: k = 74.2 [s-1 ], R2,plasma = 1.5 [s-1 ], R2,RBC = 11.6 [s-1 ], the R2 of the fit was 0.95. Average HbO2 at the SSS in seven healthy volunteers was 65% ± 7% and 66% ± 7% via T2 - and susceptometry-based oximetry, respectively. Bland-Altman analysis indicated agreement between the two oximetric methods with no significant bias. CONCLUSION The calibration constants presented here should ensure improved accuracy for whole-blood oximetry based on T2 -SSFP at 1.5T. Magn Reson Med 79:1893-1900, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

PURPOSE: To investigate the feasibility of estimating calibration constants (K and T(2o)) in vivo for converting whole-blood T(2) to blood hemoglobin oxygen saturation (HbO(2)) according to the Luz-Meiboom model, [Formula: see text] , where K and T(2o) are relaxivity and transverse relaxation time of fully saturated blood, respectively. METHODS: A range of HbO(2) values was achieved in the superficial femoral vein with intermittent cuff occlusion in seven healthy adults (four males) to establish a calibration curve between blood T(2) and HbO(2) at 1.5T. HbO(2) was derived via MR susceptometry, a technique previously validated, and the transverse relaxation time was quantified with an optimized T(2)-prepared bSSFP pulse sequence. Lastly, to evaluate the accuracy of the in vivo calibration method, T(2) and HbO(2) were quantified in the superior sagittal sinus (SSS) in six additional subjects and compared with susceptometry. RESULTS: Two sets of gender-specific calibration constants were derived, one for each gender corresponding to hematocrits (Hct) of 0.47±0.02 for males and 0.38±0.01 for females, yielding K/T(2o) = 41 Hz/260 ms and 26 Hz/280 ms, respectively. The in vivo calibration returned physiologically plausible SSS SvO(2) values (65±5%HbO(2)) and there was no significant difference between the results from the two methods (average difference −0.3%HbO(2)). CONCLUSION: The results show feasibility of performing in vivo calibration for converting whole-blood T(2) to HbO(2). The proposed approach bypasses the involved and cumbersome processes associated with in vitro calibration.

The global cerebral metabolic rate of oxygen (CMRO2), which reflects metabolic activity of the brain under various physiologic conditions, can be quantified using a method, referred to as ‘OxFlow’, which simultaneously measures hemoglobin oxygen saturation in a draining vein (Yv) and total cerebral blood flow (tCBF). Conventional OxFlow (Conv-OxFlow) entails four interleaves incorporated in a single pulse sequence – two for phase-contrast based measurement of tCBF in the supplying arteries of the neck, and two to measure the intra- to extravascular phase difference in the superior sagittal sinus to derive Yv [Jain et al, JCBFM 2010]. However, this approach limits achievable temporal resolution thus precluding capture of rapid changes of brain metabolic states such as the response to apneic stimuli. Here, we developed a time-efficient, multiplexed OxFlow method and evaluated its potential for measuring dynamic alterations in global CMRO2 during a breath-hold challenge. Two different implementations of multiplexed OxFlow were investigated: 1) simultaneous-echo-refocusing based OxFlow (SER-OxFlow) and 2) simultaneous-multi-slice imaging-based dual-band OxFlow (DB-OxFlow). The two sequences were implemented on 3T scanners (Siemens TIM Trio and Prisma) and their performance was evaluated in comparison to Conv-OxFlow in ten healthy subjects for baseline CMRO2 quantification. Comparison of measured parameters (Yv, tCBF, CMRO2) revealed no significant bias of SER-OxFlow and DB-OxFlow, with respect to the reference Conv-OxFlow while improving temporal resolution two-fold (12.5 versus 25 s). Further acceleration shortened scan time to 8 and 6 seconds for SER and DB-OxFlow, respectively, for time-resolved CMRO2 measurement. The two sequences were able of capturing smooth transitions of Yv, tCBF, and CMRO2 over the time course consisting of 30 seconds of normal breathing, 30 seconds of volitional apnea, and 90 seconds of recovery. While both SER- and DB-OxFlow techniques provide significantly improved temporal resolution (by a factor of 3 – 4 relative to Conv-OxFlow), DB-OxFlow was found to be superior for the study of short physiologic stimuli.

Feasibility study on the acquisition of lumbar spine kinematic data from upright magnetic resonance images obtained under heavy load carrying conditions.To characterize the effect of the load on spinal kinematics of active Marines under typical load carrying conditions from a macroscopic and lumbar-level approach in active-duty US Marines.Military personnel carry heavy loads of up to 68 kg depending on duty position and nature of the mission or training; these loads are in excess of the recommended assault loads. Performance and injury associated with load carriage have been studied; however, knowledge of lumbar spine kinematic changes is still not incorporated into training. These data would provide guidance for setting load and duration limits and a tool to investigate the potential contribution of heavy load carrying on lumbar spine pathologies.Sagittal T2 magnetic resonance images of the lumbar spine were acquired on a 0.6-T upright magnetic resonance imaging scanner for 10 active-duty Marines. Each Marine was scanned without load (UN1), immediately after donning load (LO2), after 45 minutes of standing (LO3) and walking (LO4) with load, and after 45 minutes of side-lying recovery (UN5). Custom-made software was used to measure whole spine angles, intervertebral angles, and regional disc heights (L1-S1). Repeated measurements analysis of variance and post hoc Sidak tests were used to identify significant differences between tasks (α = 0.05).The position of the spine was significantly (P0.0001) more horizontal relative to the external reference frame and lordosis was reduced during all tasks with load. Superior levels became more lordotic, whereas inferior levels became more kyphotic. Heavy load induced lumbar spine flexion and only anterior disc and posterior intervertebral disc height changes were observed. All kinematic variables returned to baseline levels after 45 minutes of side-lying recovery.Superior and inferior lumbar levels showed different kinematic behaviors under heavy load carrying conditions. These findings suggest a postural, lumbar flexion strategy aimed at centralizing a heavy posterior load over the base of support.

It is presumed that poor intervertebral disc cell nutrition is a contributing factor in degeneration, and is exacerbated by vertebral endplate sclerosis. Yet, quantitative relationships between endplate morphology and degeneration are unavailable. We investigated how endplate bone microstructure relates to indices of disc degeneration, such as morphologic grade, proteoglycan content, and cell density. Intervertebral core samples [n = 96, 14 subjects, L1–L5 level, ages 35–85 (64 ± 16 years), degeneration grade 1 (n = 4), grade 2 (n = 32), grade 3 (n = 44), grade 4 (n = 10), grade 5 (n = 6)] that included subchondral bone, cartilage endplate, and adjacent nucleus were harvested from human cadaveric lumbar spines. The morphology of the vertebral endplate was analyzed using µCT and the adjacent nucleus tissue was collected for biochemical and cellular analyses. Relationships between vertebral endplate morphology and adjacent disc degeneration were analyzed. Contrary to the prevailing notion, vertebral endplate porosity increased between 50% and 130% and trabecular thickness decreased by between 20% and 50% with advancing disc degeneration (p

STUDY DESIGN Experimental quantification of relationships between vertebral endplate morphology, permeability, disc cell density, glycosaminoglycan (GAG) content, and degeneration in samples harvested from human cadaveric spines. OBJECTIVE To test the hypothesis that variation in endplate permeability and porosity contributes to changes in intervertebral disc cell density and overall degeneration. SUMMARY OF BACKGROUND DATA Cells within the intervertebral disc are dependent on diffusive exchange with capillaries in the adjacent vertebral bone. Previous findings suggest that blocked routes of transport negatively affect disc quality, yet there are no quantitative relationships between human vertebral endplate permeability, porosity, cell density, and disc degeneration. Such relationships would be valuable for clarifying degeneration risk factors and patient features that may impede efforts at disc tissue engineering. METHODS Fifty-one motion segments were harvested from 13 frozen cadaveric human lumbar spines (32-85 years) and classified for degeneration using the magnetic resonance imaging-based Pfirrmann scale. A cylindrical core was harvested from the center of each motion segment that included vertebral bony and cartilage endplates along with adjacent nucleus tissue. The endplate mobility, a type of permeability, was measured directly using a custom-made permeameter before and after the cartilage endplate was removed. Cell density within the nucleus tissue was estimated using the picogreen method, while the nuclear GAG content was quantified using the dimethylmethylene blue technique. Specimens were imaged at 8 μm resolution using microCT; bony porosity was calculated. Analysis of variance, linear regression, and multiple comparison tests were used to analyze the data. RESULTS.: Nucleus cell density increased as the disc height decreased (R² = 0.13; P = 0.01) but was not related to subchondral bone porosity (P > 0.5), total mobility (P > 0.4), or age (P > 0.2). When controlling for disc height, however, a significant, negative effect of age on cell density was observed (P = 0.03). In addition to this, GAG content decreased with age nonlinearly (R² = 0.83, P < 0.0001) and a cell function measurement, GAGs/cell, decreased with degeneration (R² = 0.24; P < 0.0001). Total mobility (R² = 0.14; P < 0.01) and porosity (R² = 0.1, P < 0.01) had a positive correlation with age. CONCLUSION Although cell density increased with degeneration, cell function indicated that GAGs/cell decreased. Because permeability and porosity increase with age and degeneration, this implies that cell dysfunction, rather than physical barriers to transport, accelerates disc disease.

Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.Background: Injury to the rotator cuff can cause irreversible changes to the structure and function of the associated muscles and bones. The temporal progression and pathomechanisms associated with these adaptations are unclear. The purpose of this study was to investigate the time course of structural muscle and osseous changes in a rat model of a massive rotator cuff tear. Methods: Supraspinatus and infraspinatus muscle architecture and biochemistry and humeral and scapular morphological parameters were measured three days, eight weeks, and sixteen weeks after dual tenotomy with and without chemical paralysis via botulinum toxin A (BTX). Results: Muscle mass and physiological cross-sectional area increased over time in the age-matched control animals, decreased over time in the tenotomy1BTX group, and remained nearly the same in the tenotomy-alone group. Tenotomy1 BTX led to increased extracellular collagen in the muscle. Changes in scapular bone morphology were observed in both experimental groups, consistent with reductions in load transmission across the joint. Conclusions: These data suggest that tenotomy alone interferes with normal age-related muscle growth. The addition of chemical paralysis yielded profound structural changes to the muscle and bone, potentially leading to impaired muscle function, increased muscle stiffness, and decreased bone strength. Clinical Relevance: Structural musculoskeletal changes occur after tendon injury, and these changes are severely exacerbated with the addition of neuromuscular compromise.