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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.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).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).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.

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.

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; P0.05). CONCLUSIONS: Supraspinatus tendons detached for 1 week had shorter T2 relaxation time compared to contralateral as measured with 7T MRI.

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.

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.

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.

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.

Background and ObjectivesCoenzyme 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 CoQ10biosynthesis pathway. We report a consanguineous family presenting with a hereditary motor neuropathy associated with a homozygous c.1A > G p.? variant ofCOQ7with abnormal CoQ10biosynthesis.MethodsAffected family members underwent clinical assessments that included nerve conduction testing, histologic analysis, and MRI. Pathogenicity of theCOQ7variant was assessed in cultured fibroblasts and skeletal muscle using a combination of immunoblots, respirometry, and quinone analysis.ResultsThree 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 homozygousCOQ7c.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 theCOQ7variant was demonstrated by diminished COQ7 and CoQ10levels 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.DiscussionThis report describes a new neurologic phenotype ofCOQ7-related primary CoQ10deficiency. 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 ofCOQ7-related CoQ10deficiency previously reported in the literature.

A new CEST-MRI contrast agent, 2-HYNIC, capable of sensing aromatic aldehydes is reported. Pyridoxal 5'-phosphate, a key Vitamin B

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

In a prospective clinical trial, 20 healthy men participated in a 60-day, 6-degree head-down tilt bed rest study. Serial 3-T magnetic resonance (MR) imaging measures of the lumbar spine were performed at baseline, after 57 days of bed rest, and at 30, 360, and 720 days of reambulation (100 MR imaging scans). Proton density with and without fat saturation, 2-point Dixon, and single-voxel MR spectroscopy techniques were used to assess bone marrow composition (300 measures). Erythropoiesis was measured using hematocrit, reticulocyte, and ferritin. Also, participants randomly received either a nutritional intervention composed of polyphenols, omega-3, vitamin E, and selenium or a normal diet.Thirty days of reambulation after 60 days of bed rest caused a marked decrease of the mean lumbar vertebral fat fraction (VFF) (-9.2 ± 1.6 percentage points, -8.0 ± 1.3 percentage points, and -12.7 ± 1.2 percentage points compared with baseline using proton density, Dixon, MR spectroscopy, respectively; all 3, P0.05). Reambulation also decreased the fat saturation index (-5.3 ± 1.1 percentage points compared with baseline; P0.05). These coincided with lower hematocrit and ferritin and with increased reticulocytes at reambulation day 13 compared with baseline (all 3, P0.05). After 57 days of bed rest, the VFF was unchanged from baseline (all 3 MR techniques, P0.05); reambulation for 2 years returned the lumbar VFF to baseline values.This longitudinal trial established that 30 days of reambulation after 60 days of bed rest constituted a powerful stimulus for bone marrow reconversion. In this model, the enhanced erythropoiesis coupled with preferential consumption of fatty acids from regulated marrow adipose tissue to supply energy for erythropoiesis and bone anabolism may explain the lumbar vertebrae reconversion. These results will help interpreting bone marrow signal in ambulatory patients after long periods of bed rest.

BACKGROUND The edited magnetic resonance spectroscopy (MRS) technique has not yet been formally evaluated for the in vivo detection of 2-hydroxyglutarate (2-HG) in patients with gliomas of various grades. PURPOSE To evaluate the diagnostic accuracy of edited MRS in the preoperative identification of the isocitrate dehydrogenase (IDH) mutation status in patients with gliomas. STUDY TYPE Prospective. POPULATION Fifty-eight subjects (31 glioblastomas, 27 grade II and III gliomas). FIELD STRENGTH/SEQUENCE Mescher-Garwood (MEGA)-PRESS and routine clinical brain tumor MR sequences were used at 3T. ASSESSMENT Data were analyzed using an advanced method for accurate, robust, and efficient spectral fitting (AMARES) from jMRUI software. The amplitudes of the 2-HG, N-acetyl-aspartate (NAA), choline (Cho), and creatine/phosphocreatine (Cr) resonances were calculated with their associated Cramer-Rao lower bound (CRLB). The IDH1 R132H mutation status was assessed by immunohistochemistry for all patients. Patients with grades II and III gliomas with negative immunohistochemistry underwent DNA sequencing to further interrogate IDH mutation status. STATISTICAL TEST The differences in 2-HG amplitudes, 2-HG/NAA, 2-HG/Cho, and 2-HG/Cr between IDH-mutant and IDH-wildtype gliomas were assessed using Mann-Whitney U-tests. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic accuracy of each parameter. RESULTS The 2-HG amplitudes, 2-HG/NAA, and 2-HG/Cho were higher for IDH-mutant gliomas than IDH-wildtype gliomas (P

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.

This article reviews a body of work performed by the investigators over 9 years that has addressed the significance of cam morphology in the development of hip osteoarthritis (OA). Early hip joint degeneration is a common clinical presentation and preexisting abnormal joint morphology is a risk factor for its development. Interrogating Hill's criteria, we tested whether cam-type femoroacetabular impingement leads to hip OA. Strength of association was identified between cam morphology, reduced range-of-movement, hip pain, and cartilage degeneration. By studying a pediatric population, we were able to characterize the temporality between cam morphology (occurring 1st) and joint degeneration. Using in silico (finite element) and in vivo (imaging biomarkers) studies, we demonstrated the biological plausibility of how a cam deformity can lead to joint degeneration. Furthermore, we were able to show a biological gradient between degree of cam deformity and extent of articular damage. However, not all patients develop joint degeneration and we were able to characterize which factors contribute to this (specificity). Lastly, we were able to show that by removing the cam morphology, one could positively influence the degenerative process (experiment). The findings of this body of work show consistency and coherence with the literature. Furthermore, they illustrate how cam morphology can lead to early joint degeneration analogous to SCFE, dysplasia, and joint mal-reduction post-injury. The findings of this study open new avenues on the association between cam morphology and OA including recommendations for the study, screening, follow-up, and assessment (patient-specific) of individuals with cam morphology in order to prevent early joint degeneration. Statement of significance: By satisfying Hill's criteria, one can deduct that in some individuals, cam morphology is a cause of OA. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3125-3135, 2018.

Cam morphology in association with femoroacetabular impingement (FAI) is a recognized cause of hip pain and cartilage damage and proposed as a leading cause of arthritis. The purpose of this study was to analyze the functional and biomechanical effects of the surgical correction of the cam deformity on the degenerative process associated with FAI.Ten male patients with a mean age of 34.3 years (range, 23.1 to 46.5 years) and a mean body mass index (and standard deviation) of 26.66 ± 4.79 kg/m underwent corrective surgery for cam deformity in association with FAI. Each patient underwent a computed tomography (CT) scan to assess acetabular bone mineral density (BMD), high-resolution T1ρ magnetic resonance imaging (MRI) of the hips to assess proteoglycan content, and squatting motion analysis as well as completed self-administered functional questionnaires (Hip disability and Osteoarthritis Outcome Score [HOOS]) both preoperatively and 2 years postoperatively.At a mean follow-up of 24.5 months, improvements in functional scores and squat performance were seen. Regarding the zone of impingement in the anterosuperior quadrant of the acetabular rim, the mean change in BMD at the time of follow-up was -31.8 mg/cc (95% confidence interval [CI], -11 to -53 mg/cc) (p = 0.008), representing a 5% decrease in BMD. The anterosuperior quadrant also demonstrated a significant decrease in T1ρ values, reflecting a stabilization of the cartilage degeneration. Significant correlations were noted between changes in clinical functional scores and changes in T1ρ values (r = -0.86; p = 0.003) as well as between the BMD and maximum vertical force (r = 0.878; p = 0.021).Surgical correction of a cam deformity in patients with symptomatic FAI not only improved clinical function but was also associated with decreases in T1ρ values and BMD. These findings are the first, to our knowledge, to show that alteration of the hip biomechanics through surgical intervention improves the overall health of the hip joint.Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Developmental dysplasia of the hip is a common risk factor of early osteoarthritis (OA). Current classical non-invasive magnetic resonance imaging (MRI) methods can be used to identify qualitative, macroscopic alterations of cartilage related to gross thickness and integrity. However, these structural changes in the cartilage often manifest late in the OA progression. In the early stage of OA, changes of the biochemical composition occur in the extracellular matrix of the cartilage. This chapter discusses quantitative MRI techniques that are sensitive to these early biochemical changes in the cartilage tissue that can be used to evaluate the hip cartilage. The concepts of the most common methods for biochemical assessment of the hip cartilage (dGEMRIC, T2, T2∗ and T1ρ mapping) are introduced and their application in the context of hip dysplasia is discussed. The necessary infrastructure for setup, conduction, and evaluation of biochemical sensitive hip cartilage MR imaging is outlined. The data post-processing steps are presented, showing the necessary steps involved to generate, analyze, and interpret the quantitative cartilage maps. The quantitative MRI cartilage mapping methods discussed are promising tools for clinical researchers to examine structural and biochemical changes in the cartilage that occur in hip dysplasia.

Highlights • Diet and activity modulate vertebral marrow adipose tissue content. • Marrow adipose tissue is distributed according to a gradient including in the spine. • Diet and inactivity did not alter lumbar spine gradient of marrow adipose tissue. • The vertebral marrow adipose tissue gradient is highly preserved. • The measure of MAT gradient may serve to detect pathological situations., Context Marrow adipose tissue (MAT) has a peripheral to central distribution in adults, higher in peripheral bones. Similarly, the spine has a caudal to cephalad MAT distribution, higher in lumbar vertebras. Diet and the level of physical activities are known modulators of MAT with significant impact on bone; however, whether these can modulate the MAT gradient is unknown. Objective To measure the effect of high protein diet and bed rest interventions on the lumbar MAT gradient. Design, participants, intervention In a prospective randomized crossover trial, 10 healthy men participated in 2 consecutive campaigns of 21days head-down-tilt-bed-rest (HDTBR). They received either whey protein and potassium bicarbonate-supplemented or control diet separated by a 4-month washout period. Main outcome measure(s) Ten serial MRI measures of lumbar vertebral fat fraction (VFF) were performed at baseline, 10days and 20days of HDTBR and 3 and 28days after HDTBR of each bed rest campaign. Results The mean L5-L1 VFF difference of 4.2 ± 1.2 percentage point higher at L5 (p = 0.008) constituted a caudal to cephalad lumbar MAT gradient. High protein diet did not alter the lumbar VFF differences during both HDTBR campaigns (all time points p > 0.05). Similarly, 2 campaigns of 21days of HDTBR did not change the lumbar VFF differences (all time points p > 0.05). Conclusions This pilot study established that the lumbar vertebral MAT gradient was not altered by a high protein nor by 2 × 21days bed rest interventions. These findings demonstrated that this lack of mechanical stimulus was not an important modulator of the lumbar MAT gradient. The highly preserved MAT gradient needs to be measured in more situations of health and disease and may potentially serve to detect pathological situations.

PURPOSE To image the supraspinatus enthesis reformation of rabbit shoulders by magnetic resonance at 7 Tesla (T) using T2 mapping after surgical repair and to assess the effects of channeling aimed at enhancing enthesis reformation. MATERIALS AND METHODS In 112 rabbits, the distal supraspinatus (SSP) tendon was unilaterally detached and reattached after 1 week. At the first surgery, channeling was performed at the footprint in 64 rabbits. At the second surgery, the SSP tendon of all rabbits was re-attached to the greater tuberosity. The shoulders were harvested at 0, 1, 2, or 4 weeks after the repair surgery and were imaged at 7T. Quantitative T2 mapping was performed using multi slice two-dimensional multi-echo spin-echo sequence with fat saturation. Enthesis regions of interests were drawn on three slices at the footprint to measure T2 relaxation times. RESULTS Tendon repair (F(2, 218) = 44; P

BACKGROUND Gliomas are the most common malignant brain tumors in children and adults. A subset of these tumors harbour mutations in the enzyme isocitrate dehydrogenase (IDH) which produces the novel oncometabolite 2-hydroxyglutarate (2HG). In general, patients with an IDH mutant glioma have a longer survival—often necessitating more re-treatment sessions over the span of a patient’s life and surveillance monitoring for tumor recurrence. The need to non-invasively detect early evidence of tumor recurrence is therefore heightened in this unique subset of patients with extended survival. As magnetic resonance spectroscopy (MRS) has been demonstrated to measure biochemical components of intracranial tumors using MRI, we conducted a study in 58 pre-operative adult patients to determine if a diagnosis of IDH mutant glioma could be made confidently using imaging data. METHODS Patients underwent neuroimaging for diagnosis or preoperative planning on a 3 tesla MR scanner. A MEGA-PRESS spectral editing technique was employed. Imaging findings were directly compared to post-operative histopathologic diagnosis. RESUTLS: For all patients with gliomas from grade II to IV, detection of 2-HG with MEGA-PRESS sequence had a sensitivity between 48% and 81%, specificity between 60% and 100%, PPV between 53% and 100% and NPV between 77% and 85% depending on the CRLB threshold. Among the different metabolite ratios, a 2-HG/NAA ratio >0.034 had the highest sensitivity and specificity, 86% and 73% respectively. DISCUSSION Magnetic resonance spectroscopy (MRS) is an underused advanced MR technique that deserves consideration in pediatric neuro-oncology given its utility in non-invasively detecting malignant gliomas.

BACKGROUND: The management of asymptomatic individuals with cam femoral morphology that predisposes their hips to femoroacetabular impingement has received little attention. Such hips may have subclinical articular damage; however, whether this cartilage damage will progress is unknown as is whether any particular bone morphologies are associated with this progression. Such knowledge could help determine the natural history and guide management of such individuals. QUESTIONS/PURPOSES: The purpose of this study was to determine whether (1) asymptomatic hips with cam morphology are at risk of further cartilage degeneration (as evaluated by T1ρ); (2) T1ρ changes are predictive of symptom onset; and (3) bony morphologic parameters are associated with T1ρ signal changes. METHODS: In a prospective, longitudinal study, 17 asymptomatic volunteers/hips (16 men; 33 ± 6 years) with cam morphology underwent two T1ρ MRI scans and functional assessment (WOMAC) at recruitment and at 4 years (range, 2–6 years). Volunteers were recruited from a previous study, which reported on the prevalence of cam morphology among asymptomatic individuals using hip MRI; cam morphology was defined as an α angle ≥ 60° anterolaterally and/or ≥ 50.5° anteriorly relative to the neck axis. The differences in T1ρ values (ΔT1ρ) and relative differences (%ΔT1ρ) were calculated as: ΔT1ρ = T1ρ(Followup) – T1ρ(Initial) and %ΔT1ρ = ΔT1ρ/T1ρ(Initial). A %ΔT1ρ > 17.6% was considered clinically important. Using CT data, femoral, acetabular, and spinopelvic parameters were measured. Whether ΔT1ρ and/or %ΔT1ρ was associated with any of the bone morphologic parameters was tested using Spearman’s correlation coefficient. RESULTS: The global T1ρ in these asymptomatic hips with cam morphology remained unchanged between initial (mean, 35 ± 5 ms) and followup scans (mean, 34 ± 3 ms; p = 0.518). No differences with the numbers available in T1ρ values were seen initially between the anterolateral and posterolateral (34 ± 6 ms versus 33 ± 4 ms; p = 0.734) regions; at followup, T1 values were higher posterolaterally (36 ± 5 ms versus 32 ± 5 ms; p = 0.031). The mean global ΔT1ρ was 1 ± 5 ms (95% confidence interval, -1 to +3 ms) and the mean global %ΔT1ρ was 2% ± 13%. Two volunteers reported lower WOMAC scores; one patient exhibited a clinically important increase in %ΔT1ρ (-26%). The degree of acetabular coverage correlated with %ΔT1ρ (rho = 0.59–0.61, p = 0.002); the lesser the acetabular coverage anterolaterally, the greater the corresponding area’s T1ρ at followup. CONCLUSIONS: Although signs of posterolateral joint degeneration were detected, these were not generally associated with symptoms, and only one of the two volunteers with the onset of symptoms had a clinically important increase in %ΔT1ρ. We found that reduced acetabular coverage may increase the likelihood that preclinical cartilage degeneration will arise within 2 to 6 years; thereby reduced acetabular coverage should be considered when stratifying asymptomatic hips at risk of degeneration. Future studies should be performed with a larger cohort and include femoral version among the parameters studied. LEVEL OF EVIDENCE: Level II, diagnostic study.

This article reviews a body of work performed by the investigators over 9 years that has addressed the significance of cam morphology in the development of hip osteoarthritis (OA). Early hip joint degeneration is a common clinical presentation and preexisting abnormal joint morphology is a risk factor for its development. Interrogating Hill's criteria, we tested whether cam-type femoroacetabular impingement leads to hip OA. Strength of association was identified between cam morphology, reduced range-of-movement, hip pain, and cartilage degeneration. By studying a pediatric population, we were able to characterize the temporality between cam morphology (occurring 1st) and joint degeneration. Using in silico (finite element) and in vivo (imaging biomarkers) studies, we demonstrated the biological plausibility of how a cam deformity can lead to joint degeneration. Furthermore, we were able to show a biological gradient between degree of cam deformity and extent of articular damage. However, not all patients develop joint degeneration and we were able to characterize which factors contribute to this (specificity). Lastly, we were able to show that by removing the cam morphology, one could positively influence the degenerative process (experiment). The findings of this body of work show consistency and coherence with the literature. Furthermore, they illustrate how cam morphology can lead to early joint degeneration analogous to SCFE, dysplasia, and joint mal-reduction post-injury. The findings of this study open new avenues on the association between cam morphology and OA including recommendations for the study, screening, follow-up, and assessment (patient-specific) of individuals with cam morphology in order to prevent early joint degeneration. Statement of significance: By satisfying Hill's criteria, one can deduct that in some individuals, cam morphology is a cause of OA. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3125-3135, 2018.

Osteoarthritis (OA) is a major degenerative joint disease characterized by progressive loss of articular cartilage, synovitis, subchondral bone changes, and osteophyte formation. Currently there is no treatment for OA except temporary pain relief and end-stage joint replacement surgery. We performed a pilot study to determine the effect of kartogenin (KGN, a small molecule) on both cartilage and subchondral bone in a rat model of OA using multimodal imaging techniques. OA was induced in rats (OA and KGN treatment group) by anterior cruciate ligament transection (ACLT) surgery in the right knee joint. Sham surgery was performed on the right knee joint of control group rats. KGN group rats received weekly intra-articular injection of 125 μM KGN 1 week after surgery until week 12. All rats underwent in vivo magnetic resonance imaging (MRI) at 3, 6, and 12 weeks after surgery. Quantitative MR relaxation measures (T1ρ and T2 ) were determined to evaluate changes in articular cartilage. Cartilage and bone turnover markers (COMP and CTX-I) were determined at baseline, 3, 6, and 12 weeks. Animals were sacrificed at week 12 and the knee joints were removed for micro-computed tomography (micro-CT) and histology. KGN treatment significantly lowered the T1ρ and T2 relaxation times indicating decreased cartilage degradation. KGN treatment significantly decreased COMP and CTX-I levels indicating decreased cartilage and bone turnover rate. KGN treatment also prevented subchondral bone changes in the ACLT rat model of OA. Thus, kartogenin is a potential drug to prevent joint deterioration in post-traumatic OA. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1780-1789, 2016.

Hips with a cam deformity are at risk for early cartilage degeneration, mainly in the anterolateral region of the joint. T1ρ MRI is a described technique for assessment of proteoglycan content in hyaline cartilage and subsequently early cartilage damage. In this study, 1.5 Tesla T1ρ MRI was performed on 20 asymptomatic hips with a cam deformity and compared to 16 healthy control hips. Cam deformity was defined as an alpha angle at 1:30 o'clock position over 60° and/or at 3:00 o'clock position over 50.5°. Hip cartilage was segmented and divided into four regions of interest (ROIs): anterolateral, anteromedial, posterolateral, and posteromedial quadrants. Mean T1ρ value of the entire weight bearing cartilage in hips with a cam deformity (34.0 ± 4.6 ms) was significantly higher compared to control hips (31.3 ± 3.2 ms, p = 0.050). This difference reached significance in the anterolateral (p = 0.042) and posteromedial quadrants (p = 0.041). No significant correlation between the alpha angle and T1ρ values was detected. The results indicate cartilage damage occurs in hips with a cam deformity before symptoms occur. A significant difference in T1ρ values was found in the anterolateral quadrant, the area of direct engagement of the deformity, and in the posteromedial quadrant. To conclude, T1ρ MRI can detect early chondral damage in asymptomatic hips with a cam deformity. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1004-1009, 2016.

Adapting ways to functionalize polymer materials is becoming increasingly important to their implementation in translational biomedical sciences. By tuning the mechanical, chemical, and biological qualities of these materials, their applications can be broadened, opening the door for more advanced integration into modern medical techniques. Here, we report on a method to integrate chemical functionalizations into discrete, microscale polymer structures, which are used for tissue engineering applications, for in vivo localization, and three-dimensional manipulation. Iron oxide nanoparticles were incorporated into the polymer matrix using common photolithographic techniques to create stably functional microstructures with magnetic potential. Using magnetic resonance imaging (MRI), we can promote visualization of microstructures contained in small collections, as well as facilitate the manipulation and alignment of microtopographical cues in a realistic tissue environment. Using similar polymer functionalization techniques, fluorine-containing compounds were also embedded in the polymer matrix of photolithographically fabricated microstructures. The incorporation of fluorine-containing compounds enabled highly sensitive and specific detection of microstructures in physiologic settings using fluorine MRI techniques (19F MRI). These functionalization strategies will facilitate more reliable noninvasive tracking and characterization of microstructured polymer implants as well as have implications for remote microstructural scaffolding alignment for three-dimensional tissue engineering applications. © 2014 American Chemical Society.

Fragestellung: Die Auswirkungen einer ketogenen Diat auf das Wachstum solider Tumoren werden aktuell kontrovers diskutiert. Aus diesem Grund wurde in vitro untersucht, bei welchen Sauerstoffkonzentrationen Tumorzellen Ketonkorper (β-Hydroxybutyrat) und die beiden Metabolite Glukose und Laktat, die auch bei einer ketogenen Diat vorkommen, verstoffwechseln. Zudem wurde exemplarisch das Tumorwachstum unter einer standardisierten ketogenen Diat im Tiermodell uberpruft. Material und Methodik: Konfluente Kulturen von 6 humanen gastrointestinalen Tumorzelllinien wurden in vitro bei 21 % und 1 % Sauerstoff untersucht. Glukose, Laktat und β-Hydroxybutyrat wurden mit Standardenzymassays bestimmt. Mit einer standardisierten ketogenen Diat wurde in Kleinnagern eine physiologische Ketose ausgelost und durch subkutane Injektion von Tumorzellen das Wachstum solider Tumoren induziert. Ergebnisse: Kulturen der 6 Tumorzelllinien verstoffwechseln Ketonkorper und Laktat bei 21 %, nicht aber bei 1 % Sauerstoff; dagegen wird Glukose bei beiden Sauerstoffkonzentrationen metabolisiert. Stehen Tumorzellen bei 21 % Sauerstoff die beiden Energietrager Glukose und Laktat gleichzeitig zur Verfugung, wird zuerst Glukose und anschliesend Laktat verstoffwechselt. Unter einer ketogenen Diat entwickeln Mause eine physiologische Ketose mit signifikant erhohten Ketonkorperspiegeln. Die Tumoren dieser Mause weisen verringerte intratumorale Laktatspiegel und ein verzogertes Wachstum auf. Schlussfolgerung: Die In-vitro-Daten dieser experimentellen Arbeit unterstutzen das Konzept, dass in vivo der Stoffwechsel solider Tumoren durch die lokale Sauerstoffversorgung wesentlich beeinflusst wird. Sauerstoffkonzentrationen von 1 %, die regelhaft in soliden Tumoren vorzufinden sind (Tumorhypoxie), reichen in vitro nicht aus, damit gastrointestinale Tumorzellen Ketonkorper und Laktat verstoffwechseln; im Gegensatz zur Glukose. Um Tumorzellen in Hypoxie zum Absterben zu bringen, sollte bei ihnen daher der Glukosestoffwechsel selektiv gehemmt und zusatzlich das Glukoseangebot durch diatetische Masnahmen eingeschrankt werden.

Purpose The purpose of the present study was to test the relative performance of chemical shift-based water-fat imaging in measuring bone marrow fat fraction in the presence of trabecular bone, having as reference standard the single-voxel magnetic resonance spectroscopy (MRS). Methods Six-echo gradient echo imaging and single-voxel MRS measurements were performed on the proximal femur of seven healthy volunteers. The bone marrow fat spectrum was characterized based on the magnitude of measurable fat peaks and an a priori knowledge of the chemical structure of triglycerides, in order to accurately extract the water peak from the overlapping broad fat peaks in MRS. The imaging-based fat fraction results were then compared to the MRS-based results both without and with taking into consideration the presence of short water components in MRS. Results There was a significant underestimation of the fat fraction using the MRS model not accounting for short species with respect to the imaging-based fat fraction. A good equivalency was observed between the fat fraction using the MRS model accounting for short species and the imaging-based fat fraction (R2 = 0.87). Conclusion The consideration of the short water species effect on bone marrow fat quantification is essential when comparing MRS-based and imaging-based fat fraction results. Magn Reson Med 71:1158–1165, 2014. © 2013 Wiley Periodicals, Inc.

To assess the use of diffusion-tensor (DT) imaging of articular cartilage to detect and grade early cartilage damage in human specimens with early signs of cartilage damage.This study was approved by the institutional review board. Forty-three cartilage-on-bone samples drilled from 21 human patellae were examined with 17.6-T magnetic resonance (MR) imaging and a diffusion-weighted spin-echo sequence (spatial resolution, 50 × 100 × 800 μm). Subsequently, samples underwent histologic analysis with safranin O staining. Cartilage damage on safranin O histologic slides was quantified with Osteoarthritis Research Society International (OARSI) grades; grades ranged from 0 (healthy) to 6 (bone remodeling). Maps of longitudinal diffusivity (λ(l)), transverse diffusivity (λ(t)), mean diffusivity (MD), and fractional anisotropy (FA) were calculated. Cartilage was segmented, and region of interest (ROI) analysis was performed and compared with histologic findings. Significant differences in MR parameters between the OARSI groups were assessed with the Tukey test. The value of DT imaging in the diagnosis and grading of cartilage damage was assessed with logistic regression analysis.Samples had OARSI grades of 0 (n = 14), 1 (n = 11), 2 (n = 12), 3 (n = 4), and 4 (n = 2). Samples with an OARSI grade greater than 0 had significantly increased λ(l), λ(t), and MD (7%-25% increase) in the superficial cartilage growing deeper into cartilage with increasing OARSI grade. Samples with an OARSI grade greater than 0 showed significantly decreased FA in the deep cartilage (-25% to -35% decrease), suggesting that changes in the collagen architecture may occur early in cartilage degradation. DTI showed excellent performance in the detection of cartilage damage (accuracy, 0.95; 41 of 43 samples) and good performance in the grading of cartilage damage (accuracy, 0.74; 32 of 43 samples).DT imaging of articular cartilage can enable physicians to detect and grade early cartilage damage.

To image the supraspinatus enthesis reformation of rabbit shoulders by magnetic resonance at 7 Tesla (T) using T2 mapping after surgical repair and to assess the effects of channeling aimed at enhancing enthesis reformation.In 112 rabbits, the distal supraspinatus (SSP) tendon was unilaterally detached and reattached after 1 week. At the first surgery, channeling was performed at the footprint in 64 rabbits. At the second surgery, the SSP tendon of all rabbits was re-attached to the greater tuberosity. The shoulders were harvested at 0, 1, 2, or 4 weeks after the repair surgery and were imaged at 7T. Quantitative T2 mapping was performed using multi slice two-dimensional multi-echo spin-echo sequence with fat saturation. Enthesis regions of interests were drawn on three slices at the footprint to measure T2 relaxation times.Tendon repair (FEnthesis reformation early after surgical repair of the SSP distal tendon was characterized by increasing T2 values.2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:461-467.

Diffusion tensor magnetic resonance imaging (DT-MRI) allows a unique insight into the microstructure of highly-directional tissues. The selection of the most proper distance function for the space of diffusion tensors is crucial in enhancing the clinical application of this imaging modality. Both linear and nonlinear metrics have been proposed in the literature over the years. The debate on the most appropriate DT-MRI distance function is still ongoing. In this paper, we presented a framework to compare the Euclidean, affine-invariant Riemannian and log-Euclidean metrics using actual high-resolution DT-MRI rat heart data. We employed temporal averaging at the diffusion tensor level of three consecutive and identically-acquired DT-MRI datasets from each of five rat hearts as a means to rectify the background noise-induced loss of myocyte directional regularity. This procedure is applied here for the first time in the context of tensor distance function selection. When compared with previous studies that used a different concrete application to juxtapose the various DT-MRI distance functions, this work is unique in that it combined the following: (i) Metrics were judged by quantitative - rather than qualitative – criteria, (ii) the comparison tools were non-biased, (iii) a longitudinal comparison operation was used on a same-voxel basis. The statistical analyses of the comparison showed that the three DT-MRI distance functions tend to provide equivalent results. Hence, we came to the conclusion that the tensor manifold for cardiac DT-MRI studies is a curved space of almost zero curvature. The signal to noise ratio dependence of the operations was investigated through simulations. Finally, the “swelling effect” occurrence following Euclidean averaging was found to be too unimportant to be worth consideration.

While often thought of as a smoking drug, tobacco (Nicotiana spp.) is now considered as a plant of choice for molecular farming and biofuel production. Here, we describe a noninvasive means of deriving both the distribution of lipid and the microtopology of the submillimeter tobacco seed, founded on nuclear magnetic resonance (NMR) technology. Our platform enables counting of seeds inside the intact tobacco capsule to measure seed sizes, to model the seed interior in three dimensions, to quantify the lipid content, and to visualize lipid gradients. Hundreds of seeds can be simultaneously imaged at an isotropic resolution of 25 µm, sufficient to assess each individual seed. The relative contributions of the embryo and the endosperm to both seed size and total lipid content could be assessed. The extension of the platform to a range of wild and cultivated Nicotiana species demonstrated certain evolutionary trends in both seed topology and pattern of lipid storage. The NMR analysis of transgenic tobacco plants with seed-specific ectopic expression of the plastidial phosphoenolpyruvate/phosphate translocator, displayed a trade off between seed size and oil concentration. The NMR-based assay of seed lipid content and topology has a number of potential applications, in particular providing a means to test and optimize transgenic strategies aimed at the manipulation of seed size, seed number, and lipid content in tobacco and other species with submillimeter seeds.

Lower back pain is a common problem frequently encountered without specific biomarkers that correlate well with an individual patient's pain generators. MRI quantification of diffusion and T2 relaxation properties may provide novel insight into the mechanical and inflammatory changes that occur in the lumbosacral nerve roots in patients with lower back pain. Accurate imaging of the spinal nerve roots is difficult because of their small caliber and oblique course in all three planes. Two-dimensional in-plane imaging of the lumbosacral nerve roots requires oblique coronal imaging with large field of view (FOV) in both dimensions, resulting in severe geometric distortions using single-shot echo planar imaging (EPI) techniques. The present work describes initial success using a reduced-FOV single-shot spin-echo EPI acquisition to obtain in-plane diffusion tensor imaging (DTI) and T2 mapping of the bilateral lumbar nerve roots at the L4 level of healthy subjects, minimizing partial volume effects, breathing artifacts and geometric distortions. A significant variation in DTI and T2 mapping metrics is also reported along the course of the normal nerve root. The fractional anisotropy is statistically significantly lower in the dorsal root ganglia (0.287 ± 0.068) than in more distal regions in the spinal nerve (0.402 ± 0.040) (p

The temporal behavior of the magnetization decay caused by the local inhomogeneous magnetic field of a capillary is analyzed. Respecting the diffusion of the spins surrounding the capillary and the strength of the susceptibility difference between the capillary and the surrounding medium, it is possible to distinguish different dephasing regimes. Each dephasing regime can be related to a certain characteristic form of the magnetization decay. If the influence of the diffusion dominates, the magnetization exhibits a monotonic decay. In the opposite case of dominating influence of the susceptibility effects, the magnetization shows an oscillating behavior. It can be shown that the dephasing process is closely related to the behavior of a damped driven harmonic oscillator.

The starchy endosperm of cereals is a priori taken as a metabolically uniform tissue. By applying a noninvasive assay based on 13C/1H-magnetic resonance imaging (MRI) to barley (Hordeum vulgare) grains, we uncovered metabolic compartmentation in the endosperm. 13C-Suc feeding during grain filling showed that the primary site of Ala synthesis was the central region of the endosperm, the part of the caryopsis experiencing the highest level of hypoxia. Region-specific metabolism in the endosperm was characterized by flux balance analysis (FBA) and metabolite profiling. FBA predicts that in the central region of the endosperm, the tricarboxylic acid cycle shifts to a noncyclic mode, accompanied by elevated glycolytic flux and the accumulation of Ala. The metabolic compartmentation within the endosperm is advantageous for the grain's carbon and energy economy, with a prominent role being played by Ala aminotransferase. An investigation of caryopses with a genetically perturbed tissue pattern demonstrated that Ala accumulation is a consequence of oxygen status, rather than being either tissue specific or dependent on the supply of Suc. Hence the 13C-Ala gradient can be used as an in vivo marker for hypoxia. The combination of MRI and metabolic modeling offers opportunities for the noninvasive analysis of metabolic compartmentation in plants.

To investigate changes of diffusion tensor imaging (DTI) parameters (mean apparent diffusion coefficient [ADC], fractional anisotropy [FA], and first eigenvector) with increasing proteoglycan (PG) extraction of articular cartilage.Twelve cylindrical cartilage-on-bone samples were drilled from 4 human patellae (3 per patella). Each sample was divided into 2 pieces. One piece underwent histologic examination to assess the PG content of the native sample by safranin-O staining and its collagen architecture by polarized light microscopy. The other underwent magnetic resonance imaging (MRI) at 17.6 T for DTI measurement. After MRI, 2 of the 3 samples from each patella were immersed in a dilute trypsin solution (0.1 mg/mL), whereas the third sample was kept as a negative control in physiological saline. After incubation (6, 48, 72, and 96 hours), the samples were reimaged, stained for PG content and for the collagen orientation. Maps of ADC, FA, and the orientation of the first eigenvector as well as histology were available for each sample before and after incubation.PG loss led to increased ADC and reduced safranin-O staining from the articular surface to the bone-cartilage interface. A significant correlation (r(2) = 0.86, P0.01) was observed between the change in bulk ADC and PG loss. Regional analysis from the articular surface to the tide mark demonstrated depth dependent significant correlations of ADC and PG loss. FA and first eigenvector as well as polarized light microscopy showed only small changes in the order of magnitude of measurement errors, not correlating with PG loss.Mean diffusivity evidence by the ADC is linearly correlated to progressive PG extraction in articular cartilage. FA and the first eigenvector seem to be specific to the collagen architecture of cartilage. DTI has the potential to become a valuable biomarker for the workup of cartilage degeneration in osteoarthritis, since evaluation of the PG content and collagen architectural properties of cartilage can be performed with a single, non–contrast-enhanced proton-based MRI measurement.

Summary Seed growth and accumulation of storage products relies on the delivery of sucrose from the maternal to the filial tissues. The transport route is hidden inside the seed and has never been visualized in vivo. Our approach, based on high-field nuclear magnetic resonance and a cus- tom made 13 C ⁄ 1 H double resonant coil, allows the non-invasive imaging and monitoring of sucrose allocation within the seed. The new technique visualizes the main stream of sucrose and determines its velocity during the grain filling in barley (Hordeum vulgare L.). Quantifiable dynamic images are provided, which allow observing movement of 13 C-sucrose at a sub-milli- metre level of resolution. The analysis of genetically modified barley grains (Jekyll transgenic lines, seg8 and Riso13 mutants) demonstrated that sucrose release via the nucellar projection towards the endosperm provides an essential mean for the control of seed growth by mater- nal organism. The sucrose allocation was further determined by structural and metabolic fea- tures of endosperm. Sucrose monitoring was integrated with an in silico flux balance analysis, representing a powerful platform for non-invasive study of seed filling in crops.

To gain insights into the tumor microenvironment in primary and secondary CNS lymphomas, we applied LC/MS and GC/MS for differential metabolomic profiling of the cerebrospinal fluid (CSF) of CNS lymphoma patients compared to control subjects. Among 145 analytes identified, the majority were involved in energy metabolism; one of the most significantly upregulated metabolites in CNS lymphoma was lactate (1.8 fold, p Thus far we have applied these metabolic imaging approaches to preclinical murine models involving diffusely invasive, intracranial, patient-derived xenografts of CNS DLBCL in RAG-/- mice, to detect tumor-associated lactate production generated by infiltrating lymphoma. We demonstrated that each of these MRS approaches detect highly invasive lymphoma that is undetectable by conventional gadolinium-enhanced T1, T2 sequences, or diffusion-weighted imaging. Because of its ability to detect real-time changes in metabolic pathways, we focused on the application of HP13C pyruvate metabolic imaging as a non-invasive imaging tool for NF-kB pathway inhibition in CNS lymphoma using these models. We evaluated the metabolic response to AZ1495, a novel, CNS penetrant, orally-bioavailable inhibitor of IRAK4 kinase, comparing MYD88 wild type vs. MYD88 L265P mutant tumor models. Using a 14.1T imaging system for MR acquisition, we demonstrated similar tumor-associated production of HP 13C lactate in both MYD88wt and MY88 mutant tumors at 3 weeks post-implantation. We determined that while AZ1495 did not significantly impact lactate production in MYD88wt lymphoma, this agent significantly down-regulated tumor-associated HP pyruvate to lactate conversion (>47%) within 2 days in MYD88 mutant CNS lymphoma (p 2-fold down-modulation of NF-kB gene expression at 4h of AZ1495 therapy, including transcripts encoding LDH-A as well as the catalytic subunit of PI3K, suggesting interaction with the B cell receptor pathway. Combination AZ1495 plus ibrutinib starting d+5 was synergistic in survival prolongation compared to AZ1495 monotherapy (p Disclosures Gao: Glaxo Smith Kline: Employment. Drew:AstraZeneca: Employment. Degorce:Astra Zeneca: Employment. Mayo:Astra Zeneca: Employment. Dillman:Astra Zeneca: Employment. Anjum:Astra Zeneca: Employment. Bloecher:Astra Zeneca: Employment. Rubenstein:Celgene: Research Funding; Genentech: Research Funding.

Although essential for normal seed development in the legumes, the metabolic role of the endosperm remains uncertain. We designed noninvasive nuclear magnetic resonance tools for the in vivo study of key metabolites in the transient liquid endosperm of intact pea (Pisum sativum) seeds. The steady-state levels of sucrose, glutamine, and alanine could be monitored and their distribution within the embryo sac visualized. Seed structure was digitalized as a three-dimensional model, providing volume information for distinct seed organs. The nuclear magnetic resonance method, combined with laser microdissection, isotope labeling, in situ hybridization, and electron microscopy, was used to contrast the wild-type endosperm with that of a mutant in which embryo growth is retarded. Expression of sequences encoding amino acid and sucrose transporters was up-regulated earlier in the endosperm than in the embryo, and this activity led to the accumulation of soluble metabolites in the endosperm vacuole. The endosperm provides a temporary source of nutrition, permits space for embryo growth, and acts as a buffer between the maternal organism and its offspring. The concentration of sucrose in the endosperm vacuole is developmentally controlled, while the total amount accumulated depends on the growth of the embryo. The endosperm concentration of glutamine is a limiting factor for protein storage. The properties of the endosperm ensure that the young embryo develops within a homeostatic environment, necessary to sustain embryogenesis. We argue for a degree of metabolite-mediated control exerted by the endosperm on the growth of, and assimilate storage by, the embryo.

Osteoarthritis (OA) is a major degenerative joint disease characterized by progressive loss of articular cartilage, synovitis, subchondral bone changes, and osteophyte formation. Currently there is no treatment for OA except temporary pain relief and end-stage joint replacement surgery. We performed a pilot study to determine the effect of kartogenin (KGN, a small molecule) on both cartilage and subchondral bone in a rat model of OA using multimodal imaging techniques. OA was induced in rats (OA and KGN treatment group) by anterior cruciate ligament transection (ACLT) surgery in the right knee joint. Sham surgery was performed on the right knee joint of control group rats. KGN group rats received weekly intra-articular injection of 125 μM KGN 1 week after surgery until week 12. All rats underwent in vivo magnetic resonance imaging (MRI) at 3, 6, and 12 weeks after surgery. Quantitative MR relaxation measures (T1ρ and T2) were determined to evaluate changes in articular cartilage. Cartilage and bone turnover markers (COMP and CTX-I) were determined at baseline, 3, 6, and 12 weeks. Animals were sacrificed at week 12 and the knee joints were removed for micro-computed tomography (micro-CT) and histology. KGN treatment significantly lowered the T1ρ and T2 relaxation times indicating decreased cartilage degradation. KGN treatment significantly decreased COMP and CTX-I levels indicating decreased cartilage and bone turnover rate. KGN treatment also prevented subchondral bone changes in the ACLT rat model of OA. Thus, kartogenin is a potential drug to prevent joint deterioration in post-traumatic OA.

Hips with a cam deformity are at risk for early cartilage degeneration, mainly in the anterolateral region of the joint. T1ρ MRI is a described technique for assessment of proteoglycan content in hyaline cartilage and subsequently early cartilage damage. In this study, 1.5 Tesla T1ρ MRI was performed on 20 asymptomatic hips with a cam deformity and compared to 16 healthy control hips. Cam deformity was defined as an alpha angle at 1:30 o'clock position over 60° and/or at 3:00 o'clock position over 50.5°. Hip cartilage was segmented and divided into four regions of interest (ROIs): anterolateral, anteromedial, posterolateral, and posteromedial quadrants. Mean T1ρ value of the entire weight bearing cartilage in hips with a cam deformity (34.0 ± 4.6 ms) was significantly higher compared to control hips (31.3 ± 3.2 ms, p = 0.050). This difference reached significance in the anterolateral (p = 0.042) and posteromedial quadrants (p = 0.041). No significant correlation between the alpha angle and T1ρ values was detected. The results indicate cartilage damage occurs in hips with a cam deformity before symptoms occur. A significant difference in T1ρ values was found in the anterolateral quadrant, the area of direct engagement of the deformity, and in the posteromedial quadrant. To conclude, T1ρ MRI can detect early chondral damage in asymptomatic hips with a cam deformity. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1004-1009, 2016.

We describe the relationship between the correlation time and microscopic spatial inhomogeneities in the static magnetic field. The theory takes into account diffusion of nuclear spins in the inhomogeneous field created by magnetized objects. A simple general expression for the correlation time is obtained. It is shown that the correlation time is dependent on a characteristic length, the diffusion coefficient of surrounding medium, the permeability of the surface and the volume fraction of the magnetized objects. For specific geometries (spheres and cylinders), exact analytical expressions for the correlation time are given. The theory can be applied to contrast agents (magnetically labeled cells), capillary network, BOLD effect and so forth.

Magnetic resonance spectroscopy (MRS) techniques that use the distant dipolar field (DDF) to locally refocus inhomogeneous line-broadening promise improved spectral resolution in spatially varying fields. We investigated three possible implementations of localized DDF spectroscopy. Theoretical analysis and phantom experiments at 17.6 T showed that only localization immediately prior to acquisition provides sufficient spatial selectivity and sensitivity for in vivo applications. Spectra from an (8 mm)3 voxel of the rat brain were acquired in 25 min, and three major metabolites were resolved. In a tumor mouse model, DDF spectra with well-resolved lines can be obtained from significantly larger voxels compared to conventional localized spectroscopy. From an inhomogeneous voxel, improved spectral resolution can be obtained with DDF techniques when a sufficient number of increments are sampled along the second spectral dimension. With fewer increments, measurement time is significantly shortened, and DDF techniques can provide higher signal-to-noise ratio (SNR) efficiency. Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc.