Assessing the impact of magnetic resonance treatment simulation (MRSIM) on target volume delineation and dose to organs at risk for oropharyngeal radiotherapy

Introduction: Assessing the use of a radiation therapy (RT) planning MRI performed in the treatment position (pMRI) on target volume delineation and effect on organ at risk dose for oropharyngeal cancer patients planned with diagnostic MRI (dMRI) and CT scan. Methods: Diagnostic MRI scans were acquired for 26 patients in a neutral patient position using a 3T scanner (dMRI). Subsequent pMRI scans were acquired on the same scanner with a flat couch top and the patient in their immobilisation mask. Each series was rigidly registered to the patients planning CT scan and volumes were first completed with the CT/dMRI. The pMRI was then made available for volume modification. For the group with revised volumes, two IMRT plans were developed to demonstrate the impact of the modification. Image and registration quality was also evaluated. Results: The pMRI registration led to the modification of target volumes for 19 of 26 participants. The pMRI target volumes were larger in absolute volume resulting in reduced capacity for organ sparing. Predominantly, modifications occurred for the primary gross tumour volume (GTVp) with a mean Dice Similarity Coefficient (DSC) of 0.7 and the resulting high risk planning target volume, a mean DSC of 0.89. Both MRIs scored similarly for image quality, with the pMRI demonstrating improved registration quality and efficiency. Conclusions: A pMRI provides improvement in registration efficiency, quality and a higher degree of oncologist confidence in target delineation. These results have led to a practice change within our department, where a pMRI is acquired for all eligible oropharyngeal cancer patients.</p

A Modified Reach-to-Grasp Task in a Supine Position Shows Coordination Between Elbow and Hand Movements After Stroke

Objective: A modified reach-to-grasp task has been developed for the purpose of investigating arm-hand coordination in a supine position in the functional magnetic resonance imaging environment. The objective of this study was to investigate the kinematics of the reach-to-grasp task, in stroke and healthy participants.Design: Observational cohort study.Setting: Movement laboratory.Participants: Ten stroke participants and 10 age-matched healthy participants performed 10 repetitions of the modified reach-to-grasp task in two conditions—a natural condition and a standardized condition in a splint.Intervention: Not applicable.Main Outcome Measures: Kinematic variables of start time of transport, start time of aperture, movement duration, time of peak velocity (PV), percentage time of PV, peak deceleration (PD), percentage time of PD, peak aperture (PA), time of PA, and percentage time of PA were recorded. The correlation between key events in the grasp and transport trajectories were investigated. Performance between conditions and groups were compared.Results: Both groups demonstrated a significant correlation between the start time of aperture and the start time of transport and between the time of PA and PV in both conditions. A significant correlation was found between the time of PA and the PD in both conditions for the healthy group, but in neither condition for the stroke group. Movements by participants with stroke had a significantly longer movement duration, a smaller PV, and an earlier absolute time of PV and PD, and an earlier percentage time of PV and PD. They also had a smaller aperture than healthy participants. Wearing the splint resulted in a significantly higher PV, later absolute and percentage time of PV, PD, and PA, and a smaller PA compared to moving without the splint. The timing of transport variables time to peak velocity and time to peak deceleration, were strongest determinants of movement duration.Conclusion: The modified reach-to-grasp movement performed without the constraint of the splint, demonstrates similar motor control and coordination between the grasp and transport components of reach-to-grasp as in seated reach-to-grasp. This provides a new task that may be used to explore reach-to-grasp in the fMRI environment

Optimal single 3T MR imaging sequence for HDR brachytherapy of cervical cancer

Purpose: The superior image quality of 3 tesla (3T) magnetic resonance (MR) imaging in cervical cancer offers the potential to use a single image set for brachytherapy. This study aimed to determine a suitable single sequence for contouring tumour and organs at risk, applicator reconstruction, and treatment planning. Material and methods: A 3T (Skyra, Siemens Healthcare AG, Germany) MR imaging system with an 18 channel body matrix coil generated HDR cervical cancer brachytherapy planning images on 20 cases using plastic-based treatment applicators. Seven different T2-weighted Turbo Spin Echo (TSE) sequences including both 3D and contiguous 2D scans based on sagittal, axial (transverse), and oblique planes were analysed. Each image set was assessed for total scanning time and usefulness in tumour localization via inter- and intra-observer analysis of high-risk clinical target volume (HR CTV) contouring. Applicator reconstruction in the treatment planning system was also considered. Results: The intra-observer difference in HR CTV volumes between 2D and 3D axial-based image sets was low with an average difference of 3.1% for each observer. 2D and 3D sagittal image sets had the highest intra- and inter observer differences (over 15%). A 2D axial 'double oblique' sequence was found to produce the best intra- (average difference of 0.6%) and inter-observer (mean SD of 9.2%) consistency and greatest conformity (average 0.80). Conclusions: There was little difference between 2D and 3D-based scanning sequences; however the increased scanning time of 3D sequences have potential to introduce greater patient motion artifacts. A contiguous 2D sequence based on an axial T2-weighted turbo-spin-echo (TSE) sequence orientated in all planes of the treatment applicator provided consistent tumour delineation whilst allowing applicator reconstruction and treatment planning

Biochemical Correlations with Fatigue in Multiple Sclerosis Detected by MR 2D Localized Correlated Spectroscopy

BACKGROUND AND PURPOSE: Fatigue is the common symptom in patients with multiple sclerosis (MS), yet its pathophysiological mechanism is poorly understood. We investigated the metabolic changes in fatigue in a group of relapsing-remitting MS (RRMS) patients using MR two-dimensional localized correlated spectroscopy (2D L-COSY). METHODS: Sixteen RRMS and 16 healthy controls were included in the study. Fatigue impact was assessed with the Modified Fatigue Impact Scale (MFIS). MR 2D L-COSY data were collected from the posterior cingulate cortex. Nonparametric statistical analysis was used to calculate the changes in creatine scaled metabolic ratios and their correlations with fatigue scores. RESULTS: Compared to healthy controls, the RRMS group showed significantly higher fatigue and lower metabolic ratios for tyrosine, glutathione, homocarnosine (GSH+Hca), fucose-3, glutamine+glutamate (Glx), glycerophosphocholine (GPC), total choline, and N-acetylaspartate (NAA-2), while increased levels for isoleucine and glucose (P ≤.05). Only GPC showed positive correlation with all fatigue domains (r =.537, P ≤.05). On the other hand, Glx-upper, NAA-2, GSH+Hca, and fucose-3 showed negative correlations with all fatigue domains (r = –.345 to –.580, P ≤.05). While tyrosine showed positive correlation with MFIS (r =.499, P ≤.05), cognitive fatigue was negatively correlated with total GSH (r = –.530, P ≤.05). No correlations were found between lesion load or brain volumes with fatigue score. CONCLUSIONS: Our results suggest that fatigue in MS is strongly correlated with an imbalance in neurometabolites but not structural brain measurements.</p

Diurnal stability and long-term repeatability of neurometabolites using single voxel 1H magnetic resonance spectroscopy

Purpose: This study was designed to evaluate the diurnal stability and long-term repeatability and reliability of one-dimensional (1D) hydrogen magnetic resonance spectroscopy (1H-MRS) in vitro and in vivo at 3 T. Material and method: A standard brain phantom was used for in vitro study. In vivo diurnal evaluation involved ten healthy subjects, while repeatability study involved six subjects. MRS was acquired from posterior cingulate gyrus (PCG), and processed with LCModel. Diurnal effects were assessed with repeated measures ANOVAs, repeatability was evaluated using coefficient of variation (CV), while reliability was assessed with standard error measurement (SEM) and intra-class correlation coefficient (ICC). Results: Diurnal metabolic changes in vitro were non-significant. The intra/inter-in vitro CVs for the major metabolites; N-acetylaspartate (NAA), creatine (Cr), myo-inositol (mI), glutamate + glutamine (Glx) and total choline (tCho) were 1−3%/2−6%, respectively. Statistically significant in vivo diurnal effects were only seen for glycerophosphocholine (GPC, +10%, F = 10.6, p = 0.001) and Glx (+6%, F = 5.1, p = 0.018). The intra/inter-subject CVs for the major metabolites ranged from 2−5%/ 5−9%, respectively. The major metabolites displayed ICC ranging from 0.5−0.7 and low SEM (0.001−0.078) reflecting high reliability in detecting neurometabolites. The inter-week interval for in vivo measurements had minimal effect on metabolite ratios (F = 1.4, p = 0.09). Conclusion: In vitro MRS showed no diurnal effects and minimal variation in metabolite levels. Most PCG metabolites are not altered diurnally. The low in vivo variability of metabolite concentration supports the use of localised MRS on clinical 3 T scanners for reliable neurometabolic profiling of the brain.</p

Diurnal variability of cerebral metabolites in healthy human brain with 2D localized correlation spectroscopy (2D L-COSY)

Background: Two-dimensional localized correlation spectroscopy (2D L-COSY) is a research tool that has been applied to evaluate in vivo metabolic activity in many neurological and oncological disorders. Circadian mediators such as brain temperature, hydration, and osmotic regulation have been claimed to change metabolic profiles. Purpose: To evaluate the diurnal variability of neuro-metabolites with 2D L-COSY in healthy subjects using a 3 T scanner. Study Type: Crossover. Population/Phantom: Ten healthy subjects and magnetic resonance spectroscopy-high definition (MRS-HD) sphere or “Braino.” Field Strength/Sequence: 3 T/2D L-COSY MRS. Assessment: In vivo 2D L-COSY measurements were performed on ten healthy subjects (5 M/5F, mean age 36.1 ± 7.7 years) repeatedly at three timepoints (0700, 1200, and 1700) on the same day. in vitro evaluations were performed in a similar fashion as in vivo on Braino containing selected brain metabolites at physiological concentrations and pH. 2D L-COSY was acquired from a 27 cm3 voxel located in the posterior cingulate cortex. A total of 75 resonances were included in the analysis and spectral peak volumes were normalized to creatine. Statistical Test: One-way repeated measured analysis of variance with Bonferroni post-hoc adjustment using SPSS software. Results: In vitro data showed no statistically significant differences between different scans (P > 0.12). in vivo results showed statistically significant diurnal variations (P ≤ 0.05, F > 3.88) for 22 resonances. Bonferroni post-hoc testing showed there was statistically significant increases in metabolite ratios between 0700 and 1700 and these include different moieties of N-acetylaspartate, creatine, choline, myo-inositol, lipids, fucose, glutathione, and homocarnosine. Data Conclusion: 2D L-COSY can detect diurnal physiological variability in neuro-metabolite levels. Thus, time of the day should be considered when planning MRS studies to avoid confounding results. Level of Evidence: 1. Technical Efficacy Stage: 1. J. Magn. Reson. Imaging 2019;50:592–601.</p

Biochemical Correlations with Fatigue in Multiple Sclerosis Detected by MR 2D Localized Correlated Spectroscopy

BACKGROUND AND PURPOSE: Fatigue is the common symptom in patients with multiple sclerosis (MS), yet its pathophysiological mechanism is poorly understood. We investigated the metabolic changes in fatigue in a group of relapsing-remitting MS (RRMS) patients using MR two-dimensional localized correlated spectroscopy (2D L-COSY). METHODS: Sixteen RRMS and 16 healthy controls were included in the study. Fatigue impact was assessed with the Modified Fatigue Impact Scale (MFIS). MR 2D L-COSY data were collected from the posterior cingulate cortex. Nonparametric statistical analysis was used to calculate the changes in creatine scaled metabolic ratios and their correlations with fatigue scores. RESULTS: Compared to healthy controls, the RRMS group showed significantly higher fatigue and lower metabolic ratios for tyrosine, glutathione, homocarnosine (GSH+Hca), fucose-3, glutamine+glutamate (Glx), glycerophosphocholine (GPC), total choline, and N-acetylaspartate (NAA-2), while increased levels for isoleucine and glucose (P ≤.05). Only GPC showed positive correlation with all fatigue domains (r =.537, P ≤.05). On the other hand, Glx-upper, NAA-2, GSH+Hca, and fucose-3 showed negative correlations with all fatigue domains (r = –.345 to –.580, P ≤.05). While tyrosine showed positive correlation with MFIS (r =.499, P ≤.05), cognitive fatigue was negatively correlated with total GSH (r = –.530, P ≤.05). No correlations were found between lesion load or brain volumes with fatigue score. CONCLUSIONS: Our results suggest that fatigue in MS is strongly correlated with an imbalance in neurometabolites but not structural brain measurements.</p

Altered in vivo brain GABA and glutamate levels are associated with multiple sclerosis central fatigue

Purpose: Fatigue is a common symptom in patients with multiple sclerosis (MS) with unknown pathophysiology. Dysfunction of the GABAergic/glutamatergic pathways involving inhibitory and excitatory neurotransmitters such as γ-aminobutyric acid (GABA) and glutamine + glutamate pool (Glx) have been implicated in several neurological disorders. This study is aimed to evaluate the potential role of GABA and Glx in the origin of central fatigue in relapse remitting MS (RRMS) patients. Methods: 24 RRMS patients and 16 age- and sex-matched healthy controls (HC) were scanned using Mescher-Garwood point resolved spectroscopy (MEGA-PRESS) with a 3 T system to quantify GABA+ and Glx from prefrontal (PFC) and sensorimotor (SMC) cortices. Self-reported fatigue status was measured on all participants using the Modified Fatigue Impact Scale (MFIS). Results: RRMS patients had higher fatigue scores relative to HC (p ≤ 0.05). Compared to HC, Glx levels in RRMS patients were significantly decreased in SMC (p = 0.04). Significant correlations were found between fatigue scores and GABA+ (r = -0.531, p = 0.008) and Glx (r = 0.511, p = 0.018) in PFC. Physical fatigue was negatively correlated with GABA+ in SMC and PFC (r = -0.428 and -0.472 respectively, p ≤ 0.04) and positively with PFC Glx (r = 0.480, p = 0.028). Conclusion: The associations between fatigue and GABA + and Glx suggest that there might be dysregulation of GABAergic/glutamatergic neurotransmission in the pathophysiological mechanism of central fatigue in MS.</p

Spinal multiparametric MRI and DEXA changes over time in men with prostate cancer treated with androgen deprivation therapy: a potential imaging biomarker of treatment toxicity

Objectives: To explore changes in bone mineral density (BMD) measured by DEXA and MRS fat fraction (FF), Dixon FF, and ADC in lower spinal vertebral bodies in men with prostate cancer treated with androgen deprivation therapy (ADT). Methods: Twenty-eight men were enrolled onto a clinical trial. All received ADT. DEXA imaging was performed at baseline and 12\ua0months. L-spine MRI was done at baseline and 6\ua0months. Results: The number of patients who underwent DEXA, Dixon, ADC, and MRS at baseline/follow-up were 28/27, 28/26, 28/26, and 22/20. An increase in FF was observed from T11 to S2 (average 1\ua0%/vertebra). There was a positive correlation between baseline MRS FF and Dixon FF (r = 0.85, p 5\ua0% BMD loss after 1\ua0year had triple the percentage increase in MRS FF at 6\ua0months (61.1\ua0% vs. 20.9\ua0%, p = 0.19). Conclusions: Changes are observed on L-spine MRI after 6\ua0months of ADT. Further investigation is warranted of MRS change as a potential predictive biomarker for later BMD loss. Key Points: • Spinal marrow fat fraction increases after 6\ua0months of androgen deprivation therapy. • More inferior vertebral bodies tend to have higher fat fractions. • MRS fat fraction changes were associated with later changes in DEXA BMD

Reliability of neurometabolite detection with two-dimensional localized correlation spectroscopy at 3T

BACKGROUNDTwo-dimensional localized correlational spectroscopy (2D L-COSY) has been applied in vivo to investigate metabolic profiles in many disorders due to its ability to detect several metabolites simultaneously. Successful application of this technique depends on the reliability of the detection and understanding of the variability result from test–retest measurements.PURPOSETo evaluate the test–retest repeatability/reliability of 2D L-COSY in detecting brain metabolites in a phantom and healthy subjects in a 3T scanner.STUDY TYPETest–retest. POPULATION/PHANTOM: Six healthy subjects and magnetic resonance spectroscopy–high definition (MRS-HD) sphere or “Braino”.FIELD STRENGTH/SEQUENCE3T/2D L-COSY MRS.ASSESSMENTHealthy subjects underwent eight weekly experiments over a period of 3 months with an intersession delay of 1 month after the first four measurements. Twenty-nine neurometabolite resonances (8 diagonal, 14 cross, and 7 composite resonances) were studied using a 27 cm3 voxel from the posterior cingulate cortex. In vitro evaluations were performed in a similar manner as in vivo on a Braino phantom containing brain metabolites at physiological concentrations and pH.STATISTICAL TESTSIntra- and intersubject variability were measured. Test–retest repeatability was calculated using coefficient of variation (CV), and reliability was assessed with standard error measurement (SEM) and intraclass correlation coefficient (ICC), using SPSS software.RESULTSThe intra/inter CV for in vitro and in vivo data ranged from 0.01–0.23%/0.02–0.29% and 0.03–0.23%/0.04–0.39%, respectively. The major diagonal peaks showed ICC ranging from 0.31 to 0.93, while the ICC for cross peaks were 0.09–0.87. The SEM for in vivo data ranged from 0.0016 to 0.08. The interweek interval may have a positive effect on metabolite ratios (P = 0.08; F = 1.78).DATA CONCLUSIONThe low variability in metabolite concentration in this study shows a high level of reliability of 2D L-COSY in the human brain