Quantification of the in vivo brain ultrashort-T2* component in healthy volunteers.

PURPOSE: Recent work has shown MRI is able to measure and quantify signals of phospholipid membrane-bound protons associated with myelin in the human brain. This work seeks to develop an improved technique for characterizing this brain ultrashort- T 2 ∗ $$ {\mathrm{T}}_2\ast $$ component in vivo accounting for T 1 $$ {\mathrm{T}}_1 $$ weighting. METHODS: Data from ultrashort echo time scans from 16 healthy volunteers with variable flip angles (VFA) were collected and fitted into an advanced regression model to quantify signal fraction, relaxation time, and frequency shift of the ultrashort- T 2 ∗ $$ {\mathrm{T}}_2\ast $$ component. RESULTS: The fitted components show intra-subject differences of different white matter structures and significantly elevated ultrashort- T 2 ∗ $$ {\mathrm{T}}_2\ast $$ signal fraction in the corticospinal tracts measured at 0.09 versus 0.06 in other white matter structures and significantly elevated ultrashort- T 2 ∗ $$ {\mathrm{T}}_2\ast $$ frequency shift in the body of the corpus callosum at - $$ - $$ 1.5 versus - $$ - $$ 2.0 ppm in other white matter structures. CONCLUSION: The significantly different measured components and measured T 1 $$ {\mathrm{T}}_1 $$ relaxation time of the ultrashort- T 2 ∗ $$ {\mathrm{T}}_2\ast $$ component suggest that this method is picking up novel signals from phospholipid membrane-bound protons.

Effects of T1p Characteristics of Load-Bearing Hip Cartilage on Bilateral Knee Patellar Cartilage Subregions: Subjects With None to Moderate Radiographic Hip Osteoarthritis.

BACKGROUND: The polyarticular nature of Osteoarthritis (OA) tends to manifest in multi-joints. Associations between cartilage health in connected joints can help identify early degeneration and offer the potential for biomechanical intervention. Such associations between hip and knee cartilages remain understudied. PURPOSE: To investigate T1p associations between hip-femoral and acetabular-cartilage subregions with Intra-limb and Inter-limb patellar cartilage; whole and deep-medial (DM), deep-lateral (DL), superficial-medial (SM), superficial-lateral (SL) subregions. STUDY TYPE: Prospective. SUBJECTS: Twenty-eight subjects (age 55.1 ± 12.8 years, 15 females) with none-to-moderate hip-OA while no radiographic knee-OA. FIELD STRENGTH/SEQUENCE: 3-T, bilateral hip, and knee: 3D-proton-density-fat-saturated (PDFS) Cube and Magnetization-Prepared-Angle-Modulated-Partitioned-k-Space-Spoiled-Gradient-Echo-Snapshots (MAPSS). ASSESSMENT: Ages of subjects were categorized into Group-1 (≤40), Group-2 (41-50), Group-3 (51-60), Group-4 (61-70), Group-5 (71-80), and Group-6 (≥81). Hip T1p maps, co-registered to Cube, underwent an atlas-based algorithm to quantify femoral and acetabular subregional (R2 -R7 ) cartilage T1p . For knee Cube, a combination of V-Net architectures was used to segment the patellar cartilage and subregions (DM, DL, SM, SL). T1p values were computed from co-registered MAPSS. STATISTICAL TESTS: For Intra-and-Inter-limb, 5 optimum predictors out of 13 (Hip subregional T1p , age group, gender) were selected by univariate linear-regression, to predict outcome (patellar T1p ). The top five predictors were stepwise added to six linear mixed-effect (LME) models. In all LME models, we assume the data come from the same subject sharing the same random effect. The best-performing models (LME-modelbest ) selected via ANOVA, were tested with DM, SM, SL, and DL subregional-mean T1p . LME assumptions were verified (normality of residuals, random-effects, and posterior-predictive-checks). RESULTS: LME-modelbest (Intra-limb) had significant negative and positive fixed-effects of femoral-R5 and acetabular-R2 T1p , respectively (conditional-R2 = 0.581). LME-modelbest (Inter-limb) had significant positive fixed-effects of femoral-R3 T1p (conditional-R2 = 0.26). DATA CONCLUSION: Significant positive and negative T1p associations were identified between load-bearing hip cartilage-subregions vs. ipsilateral and contralateral patellar cartilages respectively. The effects were localized on medial subregions of Inter-limb, in particular. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Technology and Tool Development for BACPAC: Qualitative and Quantitative Analysis of Accelerated Lumbar Spine MRI with Deep-Learning Based Image Reconstruction at 3T.

OBJECTIVES: To evaluate whether combining fast acquisitions with deep-learning reconstruction can provide diagnostically useful images and quantitative assessment comparable to standard-of-care acquisitions for lumbar spine magnetic resonance imaging (MRI). METHODS: Eighteen patients were imaged with both standard protocol and fast protocol using reduced signal averages, each protocol including sagittal fat-suppressed T2-weighted, sagittal T1-weighted, and axial T2-weighted 2D fast spin-echo sequences. Fast-acquisition data was additionally reconstructed using vendor-supplied deep-learning reconstruction with three different noise reduction factors. For qualitative analysis, standard images as well as fast images with and without deep-learning reconstruction were graded by three radiologists on five different categories. For quantitative analysis, convolutional neural networks were applied to sagittal T1-weighted images to segment intervertebral discs and vertebral bodies, and disc heights and vertebral body volumes were derived. RESULTS: Based on noninferiority testing on qualitative scores, fast images without deep-learning reconstruction were inferior to standard images for most categories. However, deep-learning reconstruction improved the average scores, and noninferiority was observed over 24 out of 45 comparisons (all with sagittal T2-weighted images while 4/5 comparisons with sagittal T1-weighted and axial T2-weighted images). Interobserver variability increased with 50 and 75% noise reduction factors. Deep-learning reconstructed fast images with 50% and 75% noise reduction factors had comparable disc heights and vertebral body volumes to standard images (r2≥ 0.86 for disc heights and r2≥ 0.98 for vertebral body volumes). CONCLUSIONS: This study demonstrated that deep-learning-reconstructed fast-acquisition images have the potential to provide noninferior image quality and comparable quantitative assessment to standard clinical images.

Magnetic Resonance Imaging of the Lumbar Spine: Recommendations for Acquisition and Image Evaluation from the BACPAC Spine Imaging Working Group.

Management of patients suffering from low back pain (LBP) is challenging and requires development of diagnostic techniques to identify specific patient subgroups and phenotypes in order to customize treatment and predict clinical outcome. The Back Pain Consortium (BACPAC) Research Program Spine Imaging Working Group has developed standard operating procedures (SOPs) for spinal imaging protocols to be used in all BACPAC studies. These SOPs include procedures to conduct spinal imaging assessments with guidelines for standardizing the collection, reading/grading (using structured reporting with semi-quantitative evaluation using ordinal rating scales), and storage of images. This article presents the approach to image acquisition and evaluation recommended by the BACPAC Spine Imaging Working Group. While the approach is specific to BACPAC studies, it is general enough to be applied at other centers performing magnetic resonance imaging (MRI) acquisitions in patients with LBP. The herein presented SOPs are meant to improve understanding of pain mechanisms and facilitate patient phenotyping by codifying MRI-based methods that provide standardized, non-invasive assessments of spinal pathologies. Finally, these recommended procedures may facilitate the integration of better harmonized MRI data of the lumbar spine across studies and sites within and outside of BACPAC studies.

Synthetic Knee MRI T1p Maps as an Avenue for Clinical Translation of Quantitative Osteoarthritis Biomarkers.

A 2D U-Net was trained to generate synthetic T1p maps from T2 maps for knee MRI to explore the feasibility of domain adaptation for enriching existing datasets and enabling rapid, reliable image reconstruction. The network was developed using 509 healthy contralateral and injured ipsilateral knee images from patients with ACL injuries and reconstruction surgeries acquired across three institutions. Network generalizability was evaluated on 343 knees acquired in a clinical setting and 46 knees from simultaneous bilateral acquisition in a research setting. The deep neural network synthesized high-fidelity reconstructions of T1p maps, preserving textures and local T1p elevation patterns in cartilage with a normalized mean square error of 2.4% and Pearson's correlation coefficient of 0.93. Analysis of reconstructed T1p maps within cartilage compartments revealed minimal bias (-0.10 ms), tight limits of agreement, and quantification error (5.7%) below the threshold for clinically significant change (6.42%) associated with osteoarthritis. In an out-of-distribution external test set, synthetic maps preserved T1p textures, but exhibited increased bias and wider limits of agreement. This study demonstrates the capability of image synthesis to reduce acquisition time, derive meaningful information from existing datasets, and suggest a pathway for standardizing T1p as a quantitative biomarker for osteoarthritis.

Region of interest-specific loss functions improve T2 quantification with ultrafast T2 mapping MRI sequences in knee, hip and lumbar spine.

MRI T2 mapping sequences quantitatively assess tissue health and depict early degenerative changes in musculoskeletal (MSK) tissues like cartilage and intervertebral discs (IVDs) but require long acquisition times. In MSK imaging, small features in cartilage and IVDs are crucial for diagnoses and must be preserved when reconstructing accelerated data. To these ends, we propose region of interest-specific postprocessing of accelerated acquisitions: a recurrent UNet deep learning architecture that provides T2 maps in knee cartilage, hip cartilage, and lumbar spine IVDs from accelerated T2-prepared snapshot gradient-echo acquisitions, optimizing for cartilage and IVD performance with a multi-component loss function that most heavily penalizes errors in those regions. Quantification errors in knee and hip cartilage were under 10% and 9% from acceleration factors R = 2 through 10, respectively, with bias for both under 3 ms for most of R = 2 through 12. In IVDs, mean quantification errors were under 12% from R = 2 through 6. A Gray Level Co-Occurrence Matrix-based scheme showed knee and hip pipelines outperformed state-of-the-art models, retaining smooth textures for most R and sharper ones through moderate R. Our methodology yields robust T2 maps while offering new approaches for optimizing and evaluating reconstruction algorithms to facilitate better preservation of small, clinically relevant features.

Magnetization-prepared spoiled gradient-echo snapshot imaging for efficient measurement of R2 -R1ρ in knee cartilage.

PURPOSE: To validate the potential of quantifying R2 -R1ρ using one pair of signals with T1ρ preparation and T2 preparation incorporated to magnetization-prepared angle-modulated partitioned k-space spoiled gradient-echo snapshots (MAPSS) acquisition and to find an optimal preparation time (Tprep ) for in vivo knee MRI. METHODS: Bloch equation simulations were first performed to assess the accuracy of quantifying R2 -R1ρ using T1ρ - and T2 -prepared signals with an equivalent Tprep . For validation of this technique in comparison to the conventional approach that calculates R2 -R1ρ after estimating both T2 and T1ρ , phantom experiments and in vivo validation with five healthy subjects and five osteoarthritis patients were performed at a clinical 3T scanner. RESULTS: Bloch equation simulations demonstrated that the accuracy of this efficient R2 -R1ρ quantification method and the optimal Tprep can be affected by image signal-to-noise ratio (SNR) and tissue relaxation times, but quantification can be closest to the reference with an around 25 ms Tprep for knee cartilage. Phantom experiments demonstrated that the proposed method can depict R2 -R1ρ changes with agarose gel concentration. With in vivo data, significant correlation was observed between cartilage R2 -R1ρ measured from the conventional and the proposed methods, and a Tprep of 25.6 ms provided the most agreement by Bland-Altman analysis. R2 -R1ρ was significantly lower in patients than in healthy subjects for most cartilage compartments. CONCLUSION: As a potential biomarker to indicate cartilage degeneration, R2 -R1ρ can be efficiently measured using one pair of T1ρ -prepared and T2 -prepared signals with an optimal Tprep considering cartilage relaxation times and image SNR.

Influence of patient-specific factors when comparing multifidus fat infiltration between chronic low back pain patients and asymptomatic controls.

Introduction: Many studies have attempted to link multifidus (MF) fat infiltration with muscle quality and chronic low back pain (cLBP), but there is no consensus on these relationships. Methods: In this cross-sectional cohort study, 39 cLBP patients and 18 asymptomatic controls were included. The MF muscle was manually segmented at each lumbar disc level and fat fraction (FF) measurements were taken from the corresponding advanced imaging water-fat images. We assessed the distribution patterns of MF fat from L1L2 to L5S1 and compared these patterns between groups. The sample was stratified by age, sex, body mass index (BMI), subject-reported pain intensity (VAS), and subject-reported low back pain disability (oswestry disability index, ODI). Results: Older patients had significantly different MF FF distribution patterns compared to older controls (p < 0.0001). Male patients had 34.8% higher mean lumbar spine MF FF compared to male controls (p = 0.0006), significantly different MF FF distribution patterns (p = 0.028), 53.7% higher mean MF FF measurements at L2L3 (p = 0.037), and 50.6% higher mean MF FF measurements at L3L4 (p = 0.041). Low BMI patients had 29.7% higher mean lumbar spine MF FF compared to low BMI controls (p = 0.0077). High BMI patients only had 4% higher mean lumbar spine MF FF compared to high BMI controls (p = 0.7933). However, high BMI patients had significantly different MF FF distribution patterns compared to high BMI controls (p = 0.0324). Low VAS patients did not significantly differ from the control cohort for any of our outcomes of interest; however, high VAS patients had 24.3% higher mean lumbar spine MF FF values (p = 0.0011), significantly different MF FF distribution patterns (p < 0.0001), 34.7% higher mean MF FF at L2L3 (p = 0.040), and 34.6% higher mean MF FF at L3L4 (p = 0.040) compared to the control cohort. Similar trends were observed for ODI. Conclusions: This study suggests that when the presence of paraspinal muscle fat infiltration is not characteristic of an individual's age, sex, and BMI, it may be associated with lower back pain.

Measurement of vertebral endplate bone marrow lesion (Modic change) composition with water-fat MRI and relationship to patient-reported outcome measures.

PURPOSE: Vertebral endplate bone marrow lesions ("Modic changes", MC) are associated with chronic low back pain (CLBP). Bone marrow composition in MC is poorly understood. The goals of this study were to: (1) measure bone marrow fat fraction (BMF) in CLBP patients with MC using water-fat MRI and (2) assess the relationship between BMF measurements and patient-reported clinical characteristics. METHODS: In this cross-sectional study, 42 CLBP patients (men, n = 21; age, 48 ± 12.4 years) and 18 asymptomatic controls (men, n = 10; 42.7 ± 12.8 years) underwent 3 T MRI between January 2016 and July 2018. Imaging consisted of T1- and T2-weighted sequences to evaluate MC and spoiled gradient-recalled echo sequence with asymmetric echoes and least-squares fitting to measure BMF. BMF was compared between vertebrae with and without MC using mixed effects models. The relationship between the BMF measurements and patient-reported disability scores was examined using regression. RESULTS: Twenty-seven subjects (26 CLBP, 1 control) had MC, and MC presence coincided with significantly altered BMF. In MC 1, BMF was lower than endplates without MC (absolute difference -22.3%; p < 0.001); in MC 2, BMF was higher (absolute difference 21.0%; p < 0.001). Absolute BMF differences between affected and unaffected marrow were larger in patients with greater disability (p = 0.029-0.032) and were not associated with pain (p = 0.49-0.83). CONCLUSION: BMF is significantly altered in MC. Water-fat MRI enables BMF measurements that may eventually form the basis for quantitative assessments of MC severity and progression.

Patients with Type 2 Diabetes Exhibit a More Mineralized Deep Cartilage Layer Compared with Nondiabetic Controls: A Pilot Study.

OBJECTIVE: To assess differences in biochemical composition of the deep cartilage layer in subjects with type 2 diabetes mellitus (T2DM) and nondiabetic controls using UTE (ultra-short echo time) T2* mapping and to investigate the association of vascular health and UTE T2* measurements. DESIGN: Ten subjects with T2DM matched for age, sex, and body mass index with 10 nondiabetic controls. A 3D UTE sequence with 6 echo times was acquired using 3T magnetic resonance imaging of the knee. For UTE T2* analysis, the deep cartilage layer was segmented and analyzed in 5 compartments (patella, medial, and lateral femur and tibia). The ankle brachial index (ABI) was obtained in all subjects. Linear regression analyses were used to assess associations of T2DM and UTE T2* relaxation times and the associations of ABI measurements and UTE measurements. RESULTS: Compared with nondiabetic controls, T2DM subjects had significantly lower mean T2*-UTE in the patella (mean difference 4.87 ms; 95% confidence interval [CI] 1.09-8.65; P = 0.015), the lateral tibia (mean difference 2.26 ms; 95% CI 0.06-4.45; P = 0.045), and the lateral femur (mean difference 4.96 ms; 95% CI 0.19-9.73; P = 0.043). Independent of diabetic status, subjects with higher ABI values, indicating better vascular health, had higher T2*-UTE of the patella (coefficient 15.2; 95% CI 3.3-21.4; P = 0.017), the medial tibia (coefficient 9.8; 95% CI 1.0-18.6; P = 0.031), and the lateral femur (coefficient 18.8; 95% CI 3.3-34.3; P = 0.021). CONCLUSIONS: T2*-UTE measurements of the deep cartilage layer were consistently lower in subjects with T2DM and in subjects with impaired vascular health, likely indicating increased mineralization of this layer.

Simultaneous multi-slice spin- and gradient-echo dynamic susceptibility-contrast perfusion-weighted MRI of gliomas.

Although combined spin- and gradient-echo (SAGE) dynamic susceptibility-contrast (DSC) MRI can provide perfusion quantification that is sensitive to both macrovessels and microvessels while correcting for T1 -shortening effects, spatial coverage is often limited in order to maintain a high temporal resolution for DSC quantification. In this work, we combined a SAGE echo-planar imaging (EPI) sequence with simultaneous multi-slice (SMS) excitation and blipped controlled aliasing in parallel imaging (blipped CAIPI) at 3 T to achieve both high temporal resolution and whole brain coverage. Two protocols using this sequence with multi-band (MB) acceleration factors of 2 and 3 were evaluated in 20 patients with treated gliomas to determine the optimal scan parameters for clinical use. ΔR2 *(t) and ΔR2 (t) curves were derived to calculate dynamic signal-to-noise ratio (dSNR), ΔR2 *- and ΔR2 -based relative cerebral blood volume (rCBV), and mean vessel diameter (mVD) for each voxel. The resulting SAGE DSC images acquired using MB acceleration of 3 versus 2 appeared visually similar in terms of image distortion and contrast. The difference in the mean dSNR from normal-appearing white matter (NAWM) and that in the mean dSNR between NAWM and normal-appearing gray matter were not statistically significant between the two protocols. ΔR2 *- and ΔR2 -rCBV maps and mVD maps provided unique contrast and spatial heterogeneity within tumors.

Evaluation of human cartilage endplate composition using MRI: Spatial variation, association with adjacent disc degeneration, and in vivo repeatability.

Cartilage endplate (CEP) biochemical composition may influence disc degeneration and regeneration. However, evaluating CEP composition in patients remains a challenge. We used T2* mapping from ultrashort echo-time (UTE) magnetic resonance imaging (MRI), which is sensitive to CEP hydration, to investigate spatial variations in CEP T2* values and to determine how CEP T2* values correlate with adjacent disc degeneration. Thirteen human cadavers (56.4 ± 12.7 years) and seven volunteers (36.9 ± 10.9 years) underwent 3T MRI, including UTE and T1ρ mapping sequences. Spatial mappings of T2* values in L4-S1 CEPs were generated from UTE images and compared between subregions. In the abutting discs, mean T1ρ values in the nucleus pulposus were compared between CEPs with high vs low T2* values. To assess in vivo repeatability, precision errors in mean T2* values, and intraclass correlation coefficients (ICC) were measured from repeat scans. Results showed that CEP T2* values were highest centrally and lowest posteriorly. In the youngest individuals (<50 years), who had mild-to-moderately degenerated Pfirrmann grade II-III discs, low CEP T2* values associated with severer disc degeneration: T1ρ values were 26.7% lower in subjects with low CEP T2* values (P = .025). In older individuals, CEP T2* values did not associate with disc degeneration (P = .39-.62). Precision errors in T2* ranged from 1.7 to 2.6 ms, and reliability was good-to-excellent (ICC = 0.89-0.94). These findings suggest that deficits in CEP composition, as indicated by low T2* values, associate with severer disc degeneration during the mild-to-moderate stages. Measuring CEP T2* values with UTE MRI may clarify the role of CEP composition in patients with mild-to-moderate disc degeneration.

Investigating the Association of Metabolic Biomarkers With Knee Cartilage Composition and Structural Abnormalities Using MRI: A Pilot Study.

OBJECTIVE: The goal of this study was to explore the metabolic syndrome-associated phenotype of osteoarthritis by investigating the cross-sectional associations of glycemic markers and serum lipids with knee cartilage composition and structural abnormalities in middle-aged adults. DESIGN: Twenty participants between 40 to 70 years of age with Kellgren-Lawrence score 0-1 in at least one knee were recruited at a single center. Knee cartilage composition was assessed using 3.0 T cartilage T2 and T1ρ mapping. Evaluation of structural knee abnormalities was performed using the modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). Linear regression was used to assess the associations of standardized fasting glucose (FG), hemoglobin A1c (HbA1c), insulin, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-HDL cholesterol, and triglycerides with cartilage T2 and T1ρ as well as WORMS subscores, adjusting for body mass index. RESULTS: Higher FG and higher HbA1c were associated with higher WORMS meniscus sum (beta coefficient 1.31 [95% confidence interval (CI): 0.57, 2.05], P = 0.002 per standard deviation [SD] increase in FG; beta coefficient 0.90 [95% CI: 0.07, 1.73], P = 0.035 per SD increase in HbA1c). Also, higher total cholesterol and higher non-HDL cholesterol were associated with higher WORMS cartilage sum (beta coefficient 0.94 [95% CI: 0.01, 1.86], P = 0.048 per SD increase in total cholesterol; beta coefficient 1.05 [95% CI: 0.14, 1.96], P = 0.03 per SD increase in non-HDL cholesterol). CONCLUSIONS: Higher FG and HbA1c were associated with increased meniscal degeneration while higher total and non-HDL cholesterol were associated with increased cartilage degeneration.

Bone material analogues for PET/MRI phantoms.

PURPOSE: To develop bone material analogues that can be used in construction of phantoms for simultaneous PET/MRI systems. METHODS: Plaster was used as the basis for the bone material analogues tested in this study. It was mixed with varying concentrations of an iodinated CT contrast, a gadolinium-based MR contrast agent, and copper sulfate to modulate the attenuation properties and MRI properties (T1 and T2*). Attenuation was measured with CT and 68 Ge transmission scans, and MRI properties were measured with quantitative ultrashort echo time pulse sequences. A proof-of-concept skull was created by plaster casting. RESULTS: Undoped plaster has a 511 keV attenuation coefficient (~0.14 cm-1 ) similar to cortical bone (0.10-0.15 cm-1 ), but slightly longer T1 (~500 ms) and T2* (~1.2 ms) MR parameters compared to bone (T1 ~ 300 ms, T2* ~ 0.4 ms). Doping with the iodinated agent resulted in increased attenuation with minimal perturbation to the MR parameters. Doping with a gadolinium chelate greatly reduced T1 and T2*, resulting in extremely short T1 values when the target T2* values were reached, while the attenuation coefficient was unchanged. Doping with copper sulfate was more selective for T2* shortening and achieved comparable T1 and T2* values to bone (after 1 week of drying), while the attenuation coefficient was unchanged. CONCLUSIONS: Plaster doped with copper sulfate is a promising bone material analogue for a PET/MRI phantom, mimicking the MR properties (T1 and T2*) and 511 keV attenuation coefficient of human cortical bone.

Cortical bone vessel identification and quantification on contrast-enhanced MR images.

BACKGROUND: Cortical bone porosity is a major determinant of bone strength. Despite the biomechanical importance of cortical bone porosity, the biological drivers of cortical porosity are unknown. The content of cortical pore space can indicate pore expansion mechanisms; both of the primary components of pore space, vessels and adipocytes, have been implicated in pore expansion. Dynamic contrast-enhanced MRI (DCE-MRI) is widely used in vessel detection in cardiovascular studies, but has not been applied to visualize vessels within cortical bone. In this study, we have developed a multimodal DCE-MRI and high resolution peripheral QCT (HR-pQCT) acquisition and image processing pipeline to detect vessel-filled cortical bone pores. METHODS: For this in vivo human study, 19 volunteers (10 males and 9 females; mean age =63±5) were recruited. Both distal and ultra-distal regions of the non-dominant tibia were imaged by HR-pQCT (82 µm nominal resolution) for bone structure segmentation and by 3T DCE-MRI (Gadavist; 9 min scan time; temporal resolution =30 sec; voxel size 230×230×500 µm3) for vessel visualization. The DCE-MRI was registered to the HR-pQCT volume and the voxels within the MRI cortical bone region were extracted. Features of the DCE data were calculated and voxels were categorized by a 2-stage hierarchical kmeans clustering algorithm to determine which voxels represent vessels. Vessel volume fraction (volume ratio of vessels to cortical bone), vessel density (average vessel count per cortical bone volume), and average vessel volume (mean volume of vessels) were calculated to quantify the status of vessel-filled pores in cortical bone. To examine spatial resolution and perform validation, a virtual phantom with 5 channel sizes and an applied pseudo enhancement curve was processed through the proposed image processing pipeline. Overlap volume ratio and Dice coefficient was calculated to measure the similarity between the detected vessel map and ground truth. RESULTS: In the human study, mean vessel volume fraction was 2.2%±1.0%, mean vessel density was 0.68±0.27 vessel/mm3, and mean average vessel volume was 0.032±0.012 mm3/vessel. Signal intensity for detected vessel voxels increased during the scan, while signal for non-vessel voxels within pores did not enhance. In the validation phantom, channels with diameter 250 µm or greater were detected successfully, with volume ratio equal to 1 and Dice coefficient above 0.6. Both statistics decreased dramatically for channel sizes less than 250 µm. CONCLUSIONS: We have a developed a multi-modal image acquisition and processing pipeline that successfully detects vessels within cortical bone pores. The performance of this technique degrades for vessel diameters below the in-plane spatial resolution of the DCE-MRI acquisition. This approach can be applied to investigate the biological systems associated with cortical pore expansion.

The Relationship Between Endplate Pathology and Patient-reported Symptoms for Chronic Low Back Pain Depends on Lumbar Paraspinal Muscle Quality.

STUDY DESIGN: Cross-sectional cohort study of chronic low back pain (CLBP) patients and matched controls. OBJECTIVE: To explore the interplay between vertebral endplate damage and adjacent paraspinal muscle (PSM) quality, and to test their association in a cohort of patients with CLBP and matched controls. SUMMARY OF BACKGROUND DATA: Nonspecific CLBP is challenging to diagnose, in part, due to uncertainty regarding the source of pain. Delineating interactions among potential CLBP mechanisms may enhance diagnosis and treatment customization. METHODS: We collected advanced MRI imaging on 52 adult subjects, including 38 CLBP patients and 14 age- and sex-matched asymptomatic control subjects. Mean multifidus and erector spinae fat fraction (FF) was measured throughout the spine using an IDEAL MRI sequence. Presence of cartilage endplate (CEP) defects was determined at each disc level using UTE MRI. Logistic regression was used to test association of PSM FF, CEP defects, modic changes (MC), disc degeneration, and their interplay. RESULTS: We observed that CEP defects were the strongest predictor of nonspecific CLBP (OR: 14.1, P < 0.01) even after adjusting for MC and disc degeneration (OR: 26.1, P = 0.04). PSM quality did not independently distinguish patient and control groups, except for patients with high self-reported disability.At specifically L4L5, CEP damage was most prevalent and CEP damage was significantly associated with CLBP (OR: 3.7, 95% CI: 1.2-21.5, P = 0.03). CEP damage at L4L5 was predictive of CLBP when adjacent to PSMs with greater FF (MF, OR 14.7, P = 0.04; ES, OR: 17.3, P = 0.03), but not when PSM FF was lower and comparable to values in control, asymptomatic subjects. CONCLUSION: These results demonstrate the clinically important reciprocity between passive and dynamic spinal stabilizers, and support the notion that therapies targeting the PSMs may provide clinical benefit even in the presence of other spinal pathologies. LEVEL OF EVIDENCE: 4.

Associations between vertebral body fat fraction and intervertebral disc biochemical composition as assessed by quantitative MRI.

BACKGROUND: There is an interplay between the intervertebral disc (IVD) and the adjacent bone marrow that may play a role in the development of IVD degeneration and might influence chronic lower back pain (CLBP). PURPOSE: To apply novel quantitative MRI techniques to assess the relationship between vertebral bone marrow fat (BMF) and biochemical changes in the adjacent IVD. STUDY TYPE: Prospective. SUBJECTS: Forty-six subjects (26 female and 20 male) with a mean age of 47.3 ± 12.0 years. FIELD STRENGTH/SEQUENCE: 3 T MRI; a combined T1ρ and T2 mapping pulse sequence and a 3D spoiled gradient recalled sequence with six echoes and iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) reconstruction algorithm. ASSESSMENT: Using quantitative MRI, the vertebral BMF fraction was measured as well as the biochemical composition (proteoglycan and collagen content) of the IVD. Furthermore, clinical Pfirrmann grading, Oswestry disability index (ODI), and visual analog scale (VAS) was assessed. STATISTICAL TESTS: Mixed random effects models accounting for multiple measurements per subject were used to assess the relationships between disc measurements and BMF. RESULTS: The relationships between BMF (mean) and T1ρ /T2 (mean and SD) were significant, with P < 0.05. Significant associations (P < 0.001) were found between clinical scores (Pfirrmann, ODI, and VAS) with T1ρ /T2 (mean and SD). BMF mean was significantly related to ODI (P = 0.037) and VAS (P = 0.043), but not with Pfirrmann (P = 0.451). In contrast, BMF SD was significantly related to Pfirrmann (P = 0.000) but not to ODI (P = 0.064) and VAS (P = 0.13). DATA CONCLUSION: Our study demonstrates significant associations between BMF and biochemical changes in the adjacent IVD, both assessed by quantitative MRI; this may suggest that the conversion of hematopoietic bone marrow to fatty bone marrow impairs the supply of available nutrients to cells in the IVD and may thereby accelerate disc degeneration. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2019;50:1219-1226.

Trabecular bone microstructure is impaired in the proximal femur of human immunodeficiency virus-infected men with normal bone mineral density.

BACKGROUND: There is evidence that human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) are independent risk factors for osteoporosis and fracture which is not solely explained by changes in bone mineral density. Thus, we hypothesized that the assessment of trabecular microstructure might play an important role for bone quality in this population and might explain the increased fracture risk. In this study, we have assessed bone microstructure in the proximal femur using high-resolution magnetic resonance imaging (MRI) as well as in the extremities using high resolution peripheral quantitative computed tomography (HR-pQCT) in HIV-infected men and healthy controls and compared these findings to those based on areal bone mineral density (aBMD) derived from dual X-ray absorptiometry (DXA) which is the standard clinical parameter for the diagnosis of osteoporosis. METHODS: Eight HIV-infected men and 11 healthy age-matched controls were recruited and informed consent was obtained before each scan. High-resolution MRI of the proximal femur was performed using fully balanced steady state free precession (bSSFP) on a 3T system. Three volumes of interest at corresponding anatomic locations across all subjects were defined based on registrations of a common template. Four MR-based trabecular microstructural parameters were analyzed at each region: fuzzy bone volume fraction (f-BVF), trabecular number (Tb.N), thickness (Tb.Th), and spacing (Tb.Sp). In addition, the distal radius and distal tibia were imaged with HR-pQCT. Four HR-pQCT-based microstructural parameters were analyzed: trabecular bone volume fraction (BV/TV), Tb.N, Tb.Th, and Tb.Sp. Total hip and spine aBMD were determined from DXA. RESULTS: Microstructural bone parameters derived from MRI at the proximal femur and from HR-pQCT at the distal tibia showed significantly lower bone quality in HIV-infected patients compared to healthy controls. In contrast, DXA aBMD data showed no significant differences between HIV-infected patients and healthy controls. CONCLUSIONS: Our results suggest that high-resolution imaging is a powerful tool to assess trabecular bone microstructure and can be used to assess bone health in HIV-infected men who show no differences to healthy males by DXA aBMD. Advances in MRI technology have made microstructural imaging at the proximal femur possible. Further studies in larger patient cohorts are clearly warranted.

Cartilage Endplate Thickness Variation Measured by Ultrashort Echo-Time MRI Is Associated With Adjacent Disc Degeneration.

STUDY DESIGN: A magnetic resonance imaging study of human cadaver spines. OBJECTIVE: To investigate associations between cartilage endplate (CEP) thickness and disc degeneration. SUMMARY OF BACKGROUND DATA: Damage to the CEP is associated with spinal injury and back pain. However, CEP morphology and its association with disc degeneration have not been well characterized. METHODS: Ten lumbar motion segments with varying degrees of disc degeneration were harvested from six cadaveric spines and scanned with magnetic resonance imaging in the sagittal plane using a T2-weighted two-dimensional (2D) sequence, a three-dimensional (3D) ultrashort echo-time (UTE) imaging sequence, and a 3D T1ρ mapping sequence. CEP thicknesses were calculated from 3D UTE image data using a custom, automated algorithm, and these values were validated against histology measurements. Pfirrmann grades and T1ρ values in the disc were assessed and correlated with CEP thickness. RESULTS: The mean CEP thickness calculated from UTE images was 0.74 ±â€Š0.04 mm. Statistical comparisons between histology and UTE-derived measurements of CEP thickness showed significant agreement, with the mean difference not significantly different from zero (P = 0.32). Within-disc variation of T1ρ (standard deviation) was significantly lower for Pfirrmann grade 4 than Pfirrmann grade 3 (P < 0.05). Within-disc variation of T1ρ and adjacent CEP thickness heterogeneity (coefficient of variation) had a significant negative correlation (r = -0.65, P = 0.04). The standard deviation of T1ρand the mean CEP thickness showed a moderate positive correlation (r = 0.40, P = 0.26). CONCLUSION: This study demonstrates that quantitative measurements of CEP thickness measured from UTE magnetic resonance imaging are associated with disc degeneration. Our results suggest that variability in CEP thickness and T1ρ, rather than their mean values, may serve as valuable diagnostic markers for disc degeneration. LEVEL OF EVIDENCE: N/A.