Five-Year Serial Brain MRI Analysis of Military Members Exposed to Chronic Sub-Concussive Overpressures.

BACKGROUND: The Canadian Special Operations Forces Command conducts explosives operations and training which exposes members to explosive charges at close proximity. This 5-year longitudinal trial was conducted in follow-up to our initial trial which examined military breachers with MRI and EEG pre and post blast exposure. PURPOSE: To examine brain MRI findings in military personnel exposed to multiple repeated blast exposures. STUDY TYPE: Five-year longitudinal prospective trial. POPULATION: Ninety-two males aged 23-42 with an average of 9.4 years of blast exposure. FIELD STRENGTH/SEQUENCE: 3 T brain MRI/T1-weighted 3D with reconstruction in three planes, T2-weighted, T2-weighted fluid attenuated inversion recovery (FLAIR) 3D with reconstruction in three planes, T2-weighted gradient spin echo (GRE), saturation weighted images, DWI and ADC maps, diffusion tensor imaging. ASSESSMENT: All MRI scans were interpreted by the two neuroradiologists and one neuroradiology Fellow in a blinded fashion using a customized neuroradiology reporting form. STATISTICAL TESTS: Matching parametric statistics represented the number of participants whose brain parameters improved or deteriorated over time. Odds ratio (OR) and 95% confidence intervals (CI) were computed using log regression modeling to determine volume loss, white matter lesions, hemosiderosis, gliosis, cystic changes and enlarged Virchow Robin (VR) spaces. A Kappa (κ) statistic with a 95% CI was calculated to determine rater variability between readers. RESULTS: A significant deterioration was observed in volume loss (OR = 1.083, 95% CI 0.678-1.731, permutation test), white matter changes (OR: 0.754, 95% CI 0.442-1.284, permutation test), and enlargement of VR spaces (OR: 0.775, 95% CI 0.513-1.171). Interrater reliability was low: κ = 0.283, 0.156, and 0.557 for volume loss, white matter changes, and enlargement of VR spaces, respectively. DATA CONCLUSION: There were significant changes in brain volume, white matter lesions, and enlargement of VR spaces. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Longitudinal Brain Perfusion and Symptom Presentation Following Pediatric Concussion: A Pediatric Concussion Assessment of Rest and Exertion+MRI (PedCARE+MRI) Substudy.

Emerging evidence suggests that advanced neuroimaging modalities such as arterial spin labelling (ASL) might have prognostic utility for pediatric concussion. This study aimed to: 1) examine group differences in global and regional brain perfusion in youth with concussion or orthopedic injury (OI) at 72 h and 4 weeks post-injury; 2) examine patterns of abnormal brain perfusion within both groups and their recovery; 3) investigate the association between perfusion and symptom burden within concussed and OI youths at both time-points; and 4) explore perfusion between symptomatic and asymptomatic concussed and OI youths. Youths ages 10.00-17.99 years presenting to the emergency department with an acute concussion or OI were enrolled. ASL-magnetic resonance imaging scans were conducted at 72 h and 4 weeks post-injury to measure brain perfusion, along with completion of the Health Behavior Inventory (HBI) to measure symptoms. Abnormal perfusion clusters were identified using voxel-based z-score analysis at each visit. First, mixed analyses of covariance (ANCOVAs) investigated the Group*Time interaction on global and regional perfusion. Post hoc region of interest (ROI) analyses were performed on significant regions. Second, within-group generalized estimating equations investigated the recovery of abnormal perfusion at an individual level. Third, multiple regressions at each time-point examined the association between HBI and regional perfusion, and between HBI and abnormal perfusion volumes within the concussion group. Fourth, whole-brain one-way ANCOVAs explored differences in regional and abnormal perfusion based on symptomatic status (symptomatic vs. asymptomatic) and OIs at each time-point. A total of 70 youths with a concussion [median age (interquartile range; IQR) = 12.70 (11.67-14.35), 47.1% female] and 29 with an OI [median age (IQR) = 12.05 (11.18-13.89), 41.4% female] were included. Although no Group effect was found in global perfusion, the concussion group showed greater adjusted perfusion within the anterior cingulate cortex/middle frontal gyrus (MFG) and right MFG compared with the OI group across time-points (ps ≤ 0.004). The concussion group showed lower perfusion within the right superior temporal gyrus at both time-points and bilateral occipital gyrus at 4 weeks, (ps ≤ 0.006). The number of hypoperfused clusters was increased at 72 h compared with 4 weeks in the concussion youths (p < 0.001), but not in the OIs. Moreover, Group moderated the HBI-perfusion association within the left precuneus and superior frontal gyrus at both time-points, (ps ≤ 0.001). No association was found between HBI and abnormal perfusion volume within the concussion group at any visits. At 4 weeks, the symptomatic sub-group (n = 10) showed lower adjusted perfusion within the right cerebellum and lingual gyrus, while the asymptomatic sub-group (n = 59) showed lower adjusted perfusion within the left calcarine, but greater perfusion within the left medial orbitofrontal cortex, right middle frontal gyrus, and bilateral caudate compared with OIs. Yet, no group differences were observed in the number of abnormal perfusion clusters or volumes at any visit. The present study suggests that symptoms may be associated with changes in regional perfusion, but not abnormal perfusion levels.

Congenital tremor and myopathy secondary to novel MYBPC1 variant.

Congenital myopathy with tremor (MYOTREM) is a recently described disorder characterized by mild myopathy and a postural and intention tremor present since early infancy. MYOTREM is associated with pathogenic variants in MYBPC1 which encodes slow myosin-binding protein C, a sarcomere protein with regulatory and structural roles. Here, we describe a family with three generations of variably affected members exhibiting a novel variant in MYBPC1 (c.656 T > C, p.Leu219Pro). Among the unique features of affected family members is the persistence of tremor in sleep. We also present the first muscle magnetic resonance images for this disorder, and report muscle atrophy and fatty infiltration.

Prevalence of 'Fat-Poor' Adrenal Adenomas at Chemical-Shift MRI.

OBJECTIVE: : To determine the prevalence of 'fat-poor' adrenal adenomas at chemical-shift-MRI. MATERIALS AND METHODS: : This prospective IRB approved study identified 104 consecutive patients with 127 indeterminate adrenal masses that underwent 1.5-T chemical-shift-MRI between 2021-2023. Two blinded radiologists independently measured: 1) 2-Dimensionsal (2D) chemical-shift signal intensity (SI)-index on 2D Chemical-shift-MRI (SI-index >16.5% diagnosed presence of microscopic fat), 2) unenhanced CT attenuation (in cases where unenhanced CT was available). RESULTS: : From 127 adrenal masses, there were 94% (119/127) adenomas and 6% (8/127) other masses (2 pheochromocytoma, 5 metastases, 1 lymphoma). 98% (117/119) adenomas had SI-Index >16.5%, only 2% (2/119) adenomas were 'fat-poor' by MRI. SI-Index >16.5% was 100% specific for adenoma, all other masses had SI-Index <16.5%. Unenhanced CT was available in 43% (55/127) lesions (50 adenomas, 5 other masses). 34% (17/50) adenomas were lipid-poor (>10 HU). Percentage of adenomas with SI-Index >16.5% were: 1) ≤10 HU, 100% (33/33), 2) 11-29 HU, 100% (12/12), 3) ≥30 HU, 60% (3/5). No other masses had attenuation ≤10 HU (0/5). CONCLUSION: : Fat-poor adrenal adenomas are uncommon using 2D chemical-shift signal intensity index >16.5% at 1.5-T, occurring in approximately 2% of adenomas in this large prospective series.

The ups and downs of bone-marrow adipose tissue in space.

Knowledge is rapidly accumulating on basic roles and modulation of bone-marrow adipose tissue (BMAT). Among key modulators are physical forces on bones as exerted by gravity and exercise. Studying humans returning from space has revealed that, in addition to physical forces, local energetics within the bone marrow can play modulatory roles.

Emerging and established biomarkers of oculopharyngeal muscular dystrophy.

Oculopharyngeal muscular dystrophy (OPMD) is a rare, primarily autosomal dominant, late onset muscular dystrophy commonly presenting with ptosis, dysphagia, and subsequent weakness of proximal muscles. Although OPMD diagnosis can be confirmed with high confidence by genetic testing, the slow progression of OPMD poses a significant challenge to clinical monitoring and a barrier to assessing the efficacy of treatments during clinical trials. Accordingly, there is a pressing need for more sensitive measures of OPMD progression, particularly those which do not require a muscle biopsy. This review provides an overview of progress in OPMD biomarkers from clinical assessment, quantitative imaging, histological assessments, and genomics, as well as hypothesis-generating "omics" approaches. The ongoing search for biomarkers relevant to OPMD progression needs an integrative, longitudinal approach combining validated and experimental approaches which may include clinical, imaging, demographic, and biochemical assessment methods. A multi-omics approach to biochemical biomarker discovery could help provide context for differences found between individuals with varying levels of disease activity and provide insight into pathomechanisms and prognosis of OPMD.

Bone marrow adiposity modulation after long duration spaceflight in astronauts.

Space travel requires metabolic adaptations from multiple systems. While vital to bone and blood production, human bone marrow adipose (BMA) tissue modulation in space is unknown. Here we show significant downregulation of the lumbar vertebrae BMA in 14 astronauts, 41 days after landing from six months' missions on the International Space Station. Spectral analyses indicated depletion of marrow adipose reserves. We then demonstrate enhanced erythropoiesis temporally related to low BMA. Next, we demonstrated systemic and then, local lumbar vertebrae bone anabolism temporally related to low BMA. These support the hypothesis that BMA is a preferential local energy source supplying the hypermetabolic bone marrow postflight, leading to its downregulation. A late postflight upregulation abolished the lower BMA of female astronauts and BMA modulation amplitude was higher in younger astronauts. The study design in the extreme environment of space can limit these conclusions. BMA modulation in astronauts can help explain observations on Earth.

Direct mapping of kidney function by DCE-MRI urography using a tetrazinanone organic radical contrast agent.

Chronic kidney disease (CKD) and acute kidney injury (AKI) are ongoing global health burdens. Glomerular filtration rate (GFR) is the gold standard measure of kidney function, with clinical estimates providing a global assessment of kidney health without spatial information of kidney- or region-specific dysfunction. The addition of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to the anatomical imaging already performed would yield a 'one-stop-shop' for renal assessment in cases of suspected AKI and CKD. Towards urography by DCE-MRI, we evaluated a class of nitrogen-centered organic radicals known as verdazyls, which are extremely stable even in highly reducing environments. A glucose-modified verdazyl, glucoverdazyl, provided contrast limited to kidney and bladder, affording functional kidney evaluation in mouse models of unilateral ureteral obstruction (UUO) and folic acid-induced nephropathy (FAN). Imaging outcomes correlated with histology and hematology assessing kidney dysfunction, and glucoverdazyl clearance rates were found to be a reliable surrogate measure of GFR.

MRI texture analysis of acetabular cancellous bone can discriminate between normal, cam positive, and cam-FAI hips.

OBJECTIVES: To compare the MRI texture profile of acetabular subchondral bone in normal, asymptomatic cam positive, and symptomatic cam-FAI hips and determine the accuracy of a machine learning model for discriminating between the three hip classes. METHODS: A case-control, retrospective study was performed including 68 subjects (19 normal, 26 asymptomatic cam, 23 symptomatic cam-FAI). Acetabular subchondral bone of unilateral hip was contoured on 1.5 T MR images. Nine first-order 3D histogram and 16 s-order texture features were evaluated using specialized texture analysis software. Between-group differences were assessed using Kruskal-Wallis and Mann-Whitney U tests, and differences in proportions compared using chi-square and Fisher's exact tests. Gradient-boosted ensemble methods of decision trees were created and trained to discriminate between the three groups of hips, with percent accuracy calculated. RESULTS: Sixty-eight subjects (median age 32 (28-40), 60 male) were evaluated. Significant differences among all three groups were identified with first-order (4 features, all p ≤ 0.002) and second-order (11 features, all p ≤ 0.002) texture analyses. First-order texture analysis could differentiate between control and cam positive hip groups (4 features, all p ≤ 0.002). Second-order texture analysis could additionally differentiate between asymptomatic cam and symptomatic cam-FAI groups (10 features, all p ≤ 0.02). Machine learning models demonstrated high classification accuracy of 79% (SD 16) for discriminating among all three groups. CONCLUSION: Normal, asymptomatic cam positive, and cam-FAI hips can be discriminated based on their MRI texture profile of subchondral bone using descriptive statistics and machine learning algorithms. CLINICAL RELEVANCE STATEMENT: Texture analysis can be performed on routine MR images of the hip and used to identify early changes in bone architecture, differentiating morphologically abnormal from normal hips, prior to onset of symptoms. KEY POINTS: • MRI texture analysis is a technique for extracting quantitative data from routine MRI images. • MRI texture analysis demonstrates that there are different bone profiles between normal hips and those with femoroacetabular impingement. • Machine learning models can be used in conjunction with MRI texture analysis to accurately differentiate between normal hips and those with femoroacetabular impingement.

Novel Homozygous Variant in COQ7 in Siblings With Hereditary Motor Neuropathy.

Background and Objectives: Coenzyme Q10 (CoQ10) is an important electron carrier and antioxidant. The COQ7 enzyme catalyzes the hydroxylation of 5-demethoxyubiquinone-10 (DMQ10), the second-to-last step in the CoQ10 biosynthesis pathway. We report a consanguineous family presenting with a hereditary motor neuropathy associated with a homozygous c.1A > G p.? variant of COQ7 with abnormal CoQ10 biosynthesis. Methods: Affected family members underwent clinical assessments that included nerve conduction testing, histologic analysis, and MRI. Pathogenicity of the COQ7 variant was assessed in cultured fibroblasts and skeletal muscle using a combination of immunoblots, respirometry, and quinone analysis. Results: Three affected siblings, ranging from 12 to 24 years of age, presented with a severe length-dependent motor neuropathy with marked symmetric distal weakness and atrophy with normal sensation. Muscle biopsy of the quadriceps revealed chronic denervation pattern. An MRI examination identified moderate to severe fat infiltration in distal muscles. Exome sequencing demonstrated the homozygous COQ7 c.1A > G p.? variant that is expected to bypass the first 38 amino acid residues at the n-terminus, initiating instead with methionine at position 39. This is predicted to cause the loss of the cleavable mitochondrial targeting sequence and 2 additional amino acids, thereby preventing the incorporation and subsequent folding of COQ7 into the inner mitochondrial membrane. Pathogenicity of the COQ7 variant was demonstrated by diminished COQ7 and CoQ10 levels in muscle and fibroblast samples of affected siblings but not in the father, unaffected sibling, or unrelated controls. In addition, fibroblasts from affected siblings had substantial accumulation of DMQ10, and maximal mitochondrial respiration was impaired in both fibroblasts and muscle. Discussion: This report describes a new neurologic phenotype of COQ7-related primary CoQ10 deficiency. Novel aspects of the phenotype presented by this family include pure distal motor neuropathy involvement, as well as the lack of upper motor neuron features, cognitive delay, or sensory involvement in comparison with cases of COQ7-related CoQ10 deficiency previously reported in the literature.

Clinical Features, Non-Contrast CT Radiomic and Radiological Signs in Models for the Prediction of Hematoma Expansion in Intracerebral Hemorrhage.

PURPOSE: Rapid identification of hematoma expansion (HE) risk at baseline is a priority in intracerebral hemorrhage (ICH) patients and may impact clinical decision making. Predictive scores using clinical features and Non-Contract Computed Tomography (NCCT)-based features exist, however, the extent to which each feature set contributes to identification is limited. This paper aims to investigate the relative value of clinical, radiological, and radiomics features in HE prediction. METHODS: Original data was retrospectively obtained from three major prospective clinical trials ["Spot Sign" Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy (SPOTLIGHT)NCT01359202; The Spot Sign for Predicting and Treating ICH Growth Study (STOP-IT)NCT00810888] Patients baseline and follow-up scans following ICH were included. Clinical, NCCT radiological, and radiomics features were extracted, and multivariate modeling was conducted on each feature set. RESULTS: 317 patients from 38 sites met inclusion criteria. Warfarin use (p=0.001) and GCS score (p=0.046) were significant clinical predictors of HE. The best performing model for HE prediction included clinical, radiological, and radiomic features with an area under the curve (AUC) of 87.7%. NCCT radiological features improved upon clinical benchmark model AUC by 6.5% and a clinical & radiomic combination model by 6.4%. Addition of radiomics features improved goodness of fit of both clinical (p=0.012) and clinical & NCCT radiological (p=0.007) models, with marginal improvements on AUC. Inclusion of NCCT radiological signs was best for ruling out HE whereas the radiomic features were best for ruling in HE. CONCLUSION: NCCT-based radiological and radiomics features can improve HE prediction when added to clinical features.

Motor Band Sign in Motor Neuron Disease: A Marker for Upper Motor Neuron Involvement.

BACKGROUND AND OBJECTIVE: The prevalence and role of the motor band sign (MBS) remain unclear in motor neuron disease. We report the frequency of MBS in amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS), its correlation with clinical upper motor neuron (UMN) signs, and prognostic value in ALS. METHODS: We conducted a retrospective study of ALS, PLS, and controls with retrievable MRI between 2010 and 2018. We compared the frequencies of MBS across the three groups, and studied correlation between susceptibility-weighted MRI measurements in primary motor cortices and contralateral UMN features. Clinical outcomes were compared between ALS with and without MBS. RESULTS: Thirteen ALS, 5 PLS, and 10 controls were included (median age 60 years, IQR 54-66 years; 14/28 males). MBS was present in 9/13 (69.2%, 95% CI 38.9-89.6%) and 4/5 (80.0%, 95% CI 29.9-99.0%) of ALS and PLS, respectively, and none in controls. 2/13 (15.4%, 95% CI 2.7-46.3%) ALS and 3/5 (60.0%, 95% CI 17.0-92.7%) PLS had MBS in the absence of corticospinal T2/FLAIR hyperintensity sign. Susceptibility measurements in left motor cortices had a significantly positive correlation with contralateral UMN signs in ALS (τb = 0.628, p = 0.03). Similar but nonsignificant trends was observed for right motor cortices in ALS (τb = 0.516, p = 0.07). There were no significant differences in mRS at last follow-up, mortality, or time from symptom onset to last follow-up between ALS patients with and without MBS. CONCLUSIONS: We provide limited evidence that MBS and susceptibility quantification measurements in motor cortices may serve as surrogate markers of UMN involvement in motor neuron disease.

Quantitative vs qualitative muscle MRI: Imaging biomarker in patients with Oculopharyngeal Muscular Dystrophy (OPMD).

Oculopharyngeal muscular dystrophy (OPMD) is a genetic muscle disease causing ptosis, severe swallowing difficulties and progressive limb weakness, although atypical presentations may be difficult to diagnose. Sensitive biomarkers of disease progression in OPMD are needed to enable more effective clinical trials. This study was designed to test the feasibility of using MRI to aid OPMD diagnosis and monitor OPMD progression. Twenty-five subjects with Dixon whole-body muscle MRI were enrolled: 10 patients with genetically confirmed OPMD, 10 patients with non-OPMD muscular dystrophies, and 5 controls. Using the MRI Dixon technique, muscle fat replacement was evaluated in the tongue, serratus anterior, lumbar paraspinal, adductor magnus, and soleus muscles using quantitative and semi-quantitative rating methods. Changes were compared with muscle strength testing, dysphagia severity, use of gait aids, and presence of dysarthria. Quantitative MRI scores of muscle fat replacement in the tongue could differentiate OPMD from other muscular dystrophies and from controls. Moreover, fat fraction in the tongue correlated with clinical severity of dysphagia. This study provides preliminary support for the use of Dixon-based quantitative MRI images as outcome measures for monitoring disease progression in clinical trials and provides rationale for future prospective studies aimed at methodological refinement and covariate identification.

Biallelic SOX8 Variants Associated With Novel Syndrome With Myopathy, Skeletal Deformities, Intellectual Disability, and Ovarian Dysfunction.

Background and Objectives: The human genome contains ∼20,000 genes, each of which has its own set of complex regulatory systems to govern precise expression in each developmental stage and cell type. Here, we report a female patient with congenital weakness, respiratory failure, skeletal dysplasia, contractures, short stature, intellectual delay, respiratory failure, and amenorrhea who presented to Medical Genetics service with no known cause for her condition. Methods: Whole-exome and whole-genome sequencing were conducted, as well as investigational functional studies to assess the effect of SOX8 variant. Results: The patient was found to have biallelic SOX8 variants (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)). SOX8 is a transcriptional regulator, which is predicted to be imprinted (expressed from only one parental allele), but this has not yet been confirmed. We provide evidence that while SOX8 was maternally expressed in adult-derived fibroblasts and lymphoblasts, it was biallelically expressed in other cell types and therefore suggest that biallelic variants are associated with this recessive condition. Functionally, we showed that the paternal variant had the capacity to affect mRNA splicing while the maternal variant resulted in low levels of a truncated protein, which showed decreased binding at and altered expression of SOX8 targets. Discussion: Our findings associate SOX8 variants with this novel condition, highlight how complex genome regulation can complicate novel disease-gene identification, and provide insight into the molecular pathogenesis of this disease.

Comparison of image quality and depiction of microscopic fat at 2-D and 3-D T1-Weighted (T1W) chemical shift (dual-echo) MRI for evaluation of adrenal adenomas.

OBJECTIVE: To compare image quality and detection of microscopic fat in adrenal adenomas imaged with 2-D and 3-D chemical shift imaging (CSI) and, to derive parameters which best match 2-D and 3-D-CSI. METHODS: This two-phase, retrospective, and phantom + prospective study was IRB approved. First, a retrospective assessment of 50 consecutive adrenal adenomas imaged at 1.5 T with 2-D (TR minimum, Flip Angle [FA] 70°, TE 2.2/4.4 ms.) and 3-D (TR minimum, FA 10°, TE 2.2/4.4 ms.] CSI was performed. Second, phantom (varied fat: water concentration) experiments guided a prospective assessment of 12 consecutive adrenal adenomas imaged at 1.5 T with 3-D CSI (FA 10°, 18°). Two blinded radiologists independently evaluated: image quality, signal intensity (SI) cancellation (5-point Likert scale), and CSI-index ([SI.In.Phase-SI.Opposed.Phase/SI.In.Phase]*100). RESULTS: 2-D-CSI yielded higher image quality (p < 0.001) and, subjectively (p < 0.001) and quantitatively (p < 0.001) had more SI cancellation from microscopic fat. Proportion of adenomas with no detectable microscopic fat (3-D; 26-36% subjectively, 18-24% quantitatively [CSI-index < 16.5%] versus 2-D; 20-22% subjectively, 6-8% quantitatively) differed (p = 0.008-0.08 subjectively, 0.008-0.03 quantitatively) by CSI technique. Phantom experiments indicated 18°FA 3-D-CSI compared favorably to 70° 2-D-CSI for fat detection between 5% and 50%. In vivo, there was no differences in subjective or quantitative SI cancellation comparing 18°3D-CSI and 2D-CSI (p = 0.16-0.56 and 0.73-0.60). Greater SI cancellation occurred with 18°3D compared to 10°3D-CSI evaluated subjectively (p = 0.003-0.01). CONCLUSION: 2-D CSI has subjectively higher image quality and shows more signal intensity loss from microscopic fat in adrenal adenomas compared to 10° flip angle 3-D-CSI. Increasing the 3-D flip angle to 18° more closely matches depiction of microscopic fat to 2-D-CSI at 1.5 T.

Utility of Quantitative T2-Mapping Compared to Conventional and Advanced Diffusion Weighted Imaging Techniques for Multiparametric Prostate MRI in Men with Hip Prosthesis.

BACKGROUND: Diffusion weighted imaging (DWI) is fundamental for prostate cancer (PCa) detection with MRI; however, limited by susceptibility artifact from hip prosthesis. PURPOSE: To evaluate image quality and ability to detect PCa with quantitative T2-mapping and DWI in men with hip prosthesis undergoing prostate MRI. STUDY TYPE: Prospective, cross-sectional study. POPULATION: Thirty consecutive men with hip replacement (18 unilateral, 12 bilateral) undergoing prostate MRI from 2019 to 2021. FIELD STRENGTH/SEQUENCE: 3-T; multiparametric MRI (T2W, DCE-MRI, echo-planar [EPI]-DWI), T2-mapping (Carr-Purcell-Meiboom-Gill), FOCUS-EPI-DWI, PROPELLER-DWI. ASSESSMENT: Five blinded radiologists independently evaluated MRI image quality using a 5-point Likert scale. PI-RADS v2.1 scores were applied in four interpretation strategies: 1) T2W-FSE+DCE-MRI+EPI-DWI, 2) T2W-FSE+DCE-MRI+EPI-DWI+FOCUS-EPI-DWI, 3) T2W-FSE+DCE-MRI+EPI-DWI+PROPELLER-DWI, 4) T2W-FSE+DCE-MRI+EPI-DWI+T2-maps. Five-point confidence scores were recorded. STATISTICAL ANALYSIS: ANOVA, Kruskal-Wallis with pair-wise comparisons by Wilcoxon sign-rank, and paired t-tests, P < 0.05 was considered significant. Cohen's Kappa (k) for PI-RADSv2.1 scoring and proportion of correctly classified lesions tabulated for pathology-confirmed cases with 95% confidence intervals (CIs). RESULTS: For all radiologists, T2-map image quality was significantly higher than EPI-DWI, FOCUS-EPI-DWI, and PROPELLER-DWI and similar (P = 0.146-0.706) or significantly better (for two readers) than T2W-FSE and DCE-MRI. PI-RADS v2.1 agreement improved comparing strategy A (k = 0.46) to strategy B (k = 0.58) to strategy C (k = 0.58) and was highest with strategy D which included T2-maps (k = 1.00). Radiologists' confidence was significantly highest with strategy D. Strategies B and C had similar confidence (P = 0.051-0.063) both significantly outperforming strategy A. Twelve men with 17 lesions had pathology confirmed diagnoses (13 PCa, 4 benign). Strategy D had the highest proportion of correctly classified lesions (76.5-82.4%) with overlapping 95% confidence intervals. DATA CONCLUSION: T2-mapping may be a valuable adjunct to prostate MRI in men with hip replacement resulting in improved image quality, higher reader confidence, interobserver agreement, and accuracy in PI-RADS scoring. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Mapping vitamin B6 metabolism by hydrazoCEST magnetic resonance imaging.

A new CEST-MRI contrast agent, 2-HYNIC, capable of sensing aromatic aldehydes is reported. Pyridoxal 5'-phosphate, a key Vitamin B6 metabolite necessary for >140 biotransformations was mapped by CEST-MRI in vitro and in vivo in lung cancer. 2-HYNIC provided access to this key biomarker associated with a variety of human diseases.

Quantitative analysis of repaired rabbit supraspinatus tendons (± channeling) using magnetic resonance imaging at 7 Tesla.

BACKGROUND: The quantitative assessment of supraspinatus tendons by conventional magnetic resonance is limited by low contrast-to-noise ratio (CNR). Magnetic resonance imaging (MRI) scanners operating at 7 Tesla offer high signal-to noise ratio (SNR), low CNR and high spatial resolution that are well-suited for rapidly relaxing tissues like tendons. Few studies have applied T2 and T2* mapping to musculoskeletal imaging and to the rotator cuff tendons. Our objective was to analyze the T2 and T2* relaxation times from surgically repaired supraspinatus tendons and the effect of bone channeling. METHODS: One supraspinatus tendon of 112 adult female New Zealand white rabbits was surgically detached and repaired one week later. Rabbits were randomly assigned to channeling (n=64) or control (n=48) groups and harvested at 0, 1, 2, and 4 weeks. A 7T magnet was used for signal acquisition. For T2 mapping, a sagittal multi slice 2D multi-echo spin-echo (MESE) CPMG sequence with fat saturation was applied and T2* mapping was performed using a 3D UTE sequence. Magnetic resonance images from supraspinatus tendons were analyzed by two raters. Three regions of interest were manually drawn on the first T2-weighted dataset. For T2 and T2*, different ROI masks were generated to obtain relaxation times. RESULTS: T2-weighted maps but not T2*-weighted maps generated reliable signals for relaxation time measurement. Torn supraspinatus tendons had lower T2 than controls at the time of repair (20.0±3.4 vs. 25.6±3.9 ms; P<0.05). T2 increased at 1, 2 and 4 postoperative weeks: 22.7±3.1, 23.3±3.9 and 24.0±5.1 ms, respectively, and values were significantly different from contralateral supraspinatus tendons (24.8±3.1; 26.8±4.3 and 26.5±3.6 ms; all P<0.05). Bone channeling did not affect T2 (P>0.05). CONCLUSIONS: Supraspinatus tendons detached for 1 week had shorter T2 relaxation time compared to contralateral as measured with 7T MRI.

What Is the Correlation Among dGEMRIC, T1p, and T2* Quantitative MRI Cartilage Mapping Techniques in Developmental Hip Dysplasia?

BACKGROUND: Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is a validated technique for evaluating cartilage health in developmental dysplasia of the hip (DDH), which can be a helpful prognosticator for the response to surgical treatments. dGEMRIC requires intravenous injection of gadolinium contrast, however, which adds time, expense, and possible adverse reactions to the imaging procedure. Newer MRI cartilage mapping techniques such as T1 rho (ρ) and T2* have been performed in the hip without the need for any contrast, although it is unknown whether they are equivalent to dGEMRIC. QUESTION/PURPOSE: In this study, our purpose was to determine the correlation between the relaxation values of three cartilage mapping techniques, dGEMRIC, T1ρ, and T2*, in patients with DDH. METHODS: Fifteen patients with DDH (three male, 12 female; mean age 29 ± 9 years) scheduled for periacetabular osteotomy underwent preoperative dGEMRIC, T1ρ, and T2* MRI at 3T with quantitative cartilage mapping. The outcomes of dGEMRIC, T1ρ, and T2* mapping were calculated for three regions of interest (ROI) to analyze the weightbearing cartilage of the hip: global ROI, anterior and posterior ROI, and further subdivided into medial, intermediate, and lateral to generate six smaller ROIs. The correlation between the respective relaxation time values was evaluated using the Spearman correlation coefficient (rS) for each ROI, categorized as negligible, weak, moderate, strong, or very strong. The relaxation values within the subdivided ROIs were compared for each of the three cartilage mapping techniques using the Kruskal-Wallis test. RESULTS: There was a moderate correlation of T1ρ and T2* relaxation values with dGEMRIC relaxation values. For the global ROI, there was a moderate correlation between dGEMRIC and T2* (moderate; rS = 0.63; p = 0.01). For the anterior ROI, a moderate or strong correlation was found between dGEMRIC and both T1ρ and T2*: dGEMRIC and T1ρ (strong; rS = -0.71; p = 0.003) and dGEMRIC and T2* (moderate; rS = 0.69; p = 0.004). There were no correlations for the posterior ROI. The mean dGEMRIC, T1ρ, and T2* relaxation values were not different between the anterior and posterior ROIs nor between the subdivided six ROIs. CONCLUSION: Quantitative T1ρ and T2* cartilage mapping demonstrated a moderate correlation with dGEMRIC, anteriorly and globally, respectively. However, the clinical relevance of such a correlation remains unclear. Further research investigating the correlation of these two noncontrast techniques with clinical function and outcome scores is needed before broad implementation in the preoperative investigation of DDH. LEVEL OF EVIDENCE: Level II, diagnostic study.

Quantitative Prostate MRI.

Prostate MRI is reported in clinical practice using the Prostate Imaging and Data Reporting System (PI-RADS). PI-RADS aims to standardize, as much as possible, the acquisition, interpretation, reporting, and ultimately the performance of prostate MRI. PI-RADS relies upon mainly subjective analysis of MR imaging findings, with very few incorporated quantitative features. The shortcomings of PI-RADS are mainly: low-to-moderate interobserver agreement and modest accuracy for detection of clinically significant tumors in the transition zone. The use of a more quantitative analysis of prostate MR imaging findings is therefore of interest. Quantitative MR imaging features including: tumor size and volume, tumor length of capsular contact, tumor apparent diffusion coefficient (ADC) metrics, tumor T1 and T2 relaxation times, tumor shape, and texture analyses have all shown value for improving characterization of observations detected on prostate MRI and for differentiating between tumors by their pathological grade and stage. Quantitative analysis may therefore improve diagnostic accuracy for detection of cancer and could be a noninvasive means to predict patient prognosis and guide management. Since quantitative analysis of prostate MRI is less dependent on an individual users' assessment, it could also improve interobserver agreement. Semi- and fully automated analysis of quantitative (radiomic) MRI features using artificial neural networks represent the next step in quantitative prostate MRI and are now being actively studied. Validation, through high-quality multicenter studies assessing diagnostic accuracy for clinically significant prostate cancer detection, in the domain of quantitative prostate MRI is needed. This article reviews advances in quantitative prostate MRI, highlighting the strengths and limitations of existing and emerging techniques, as well as discussing opportunities and challenges for evaluation of prostate MRI in clinical practice when using quantitative assessment. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.