Proton MR Spectroscopy Research Articles

The probably use of MR-spectroscopy and diffusion weighted-MRI of bone marrow for treatment monitoring in patients with chronic lymphatic leukemia

Objectives: To assess the usefulness of proton MR-spectroscopy (1H-MRS) and diffusion-weighted MRI (DW-MRI) sequences in the follow-up of CLL-patients with chemotherapy treatment. The monitoring of CLL-patients susceptible to chemotherapy treatment is complicated due to the difficulty in assessing the response to treatment. Chemotherapy leads to changes in bone marrow composition and these changes can be evaluated by functional MR-sequences. Methods: 23 patients diagnosed with CLL by our hospital’s Hematology Service underwent a lumbar MR prior and post-chemotherapy applying 1H-MRS and DW-MRI. The concentrations of water and lipids were quantified applying the quantification program LCModel. The Apparent Diffusion Coefficient (ADC) values were calculated with the Functool program (GE). The Wilcoxon sign test was used to compare pre and post treatment results, considering statistically significant P values lower than 0.05. Results: Responder patients decreased the ratio H2O/lipids concentration measured with 1H-MRS and increased the ADC value on DW-MRI in post-treatment studies (P<0.05). Patients without response increased the ratio and decreased the ADC values or did not modify the data. Conclusion: 1H-MRS and DW-MRI of spinal bone marrow are non-invasive and repeatable techniques that might help in follow-up monitoring of patients with CLL.

Proton MR Spectroscopy in Differenating Low Grade Glioma and Glioblastoma Multiform.

Proton MR Spectroscopy in Differenating Low Grade Glioma and Glioblastoma Multiform.

SPectroscOpic prediction of bRain Tumours (SPORT): study protocol of a prospective imaging trial

BackgroundThe revised 2016 WHO-Classification of CNS-tumours now integrates molecular information of glial brain tumours for accurate diagnosis as well as for the development of targeted therapies. In this prospective study, our aim is to investigate the predictive value of MR-spectroscopy in order to establish a solid preoperative molecular stratification algorithm of these tumours. We will process a 1H MR-spectroscopy sequence within a radiomics analytics pipeline.MethodsPatients treated at our institution with WHO-Grade II, III and IV gliomas will receive preoperative anatomical (T2- and T1-weighted imaging with and without contrast enhancement) and proton MR spectroscopy (MRS) by using chemical shift imaging (MRS) (5 × 5 × 15 mm3 voxel size). Tumour regions will be segmented and co-registered to corresponding spectroscopic voxels.Raw signals will be processed by a deep-learning approach for identifying patterns in metabolic data that provides information with respect to the histological diagnosis as well patient characteristics obtained and genomic data such as target sequencing and transcriptional data.DiscussionBy imaging the metabolic profile of a glioma using a customized chemical shift 1H MR spectroscopy sequence and by processing the metabolic profiles with a machine learning tool we intend to non-invasively uncover the genetic signature of gliomas. This work-up will support surgical and oncological decisions to improve personalized tumour treatment.Trial registrationThis study was initially registered under another name and was later retrospectively registered under the current name at the German Clinical Trials Register (DRKS) under DRKS00019855.

1H MR Spectroscopy of Fine-Needle Aspiration Biopsy Specimens for the Discrimination of Breast Cancer.

To determine whether MR spectroscopic assessment of fine-needle aspiration (FNA) biopsy specimens from suspicious breast lesions could be used to improve the diagnostic utility of FNA biopsies for the characterization of breast lesions. In this prospective study, a previously reported technique using high-spatial-resolution proton MR spectroscopy was modified and used to examine the utility of FNA biopsies in the evaluation of suspicious breast lesions. Tissue samples from 115 lesions (from 102 women; average age, 54 years) were excised by using FNA and core biopsies and were collected between September 7, 2012, and April 11, 2014. Histologic results from core biopsy specimens determined the lesions to be benign (n = 55), invasive ductal carcinoma (n = 51), invasive lobular carcinoma (n = 5), or ductal carcinoma in situ (n = 4). Measures of phosphocholine (PC), glycerophosphocholine, and choline relative to each other and to total creatine (tCr) were obtained from usable spectra. Planned comparisons among lesion groups were carried out using t test contrasts, and differences of each contrast level from zero were judged significant when the two-tailed P value was less than .05. Of the 115 samples, 69 (60%) yielded no usable MR spectra. Analysis of the 46 with usable spectra found that only the difference in PC/tCr between benign and cancer lesions was statistically significant (P = .028). Given that 60% of FNA biopsy specimens yielded no usable spectra and that results were largely inconclusive when derived from usable spectra, the combined MR and FNA technique, as modified and implemented in this study, is of little value for detection and diagnosis of breast cancer.Keywords: Breast, MR-Spectroscopy, Neoplasms-Primary© RSNA, 2020.

The neurometabolic profiles of GABA and Glutamate as revealed by proton magnetic resonance spectroscopy in type 1 and type 2 diabetes.

Glucose metabolism is pivotal for energy and neurotransmitter synthesis and homeostasis, particularly in Glutamate and GABA systems. In turn, the stringent control of inhibitory/excitatory tonus is known to be relevant in neuropsychiatric conditions. Glutamatergic neurotransmission dominates excitatory synaptic functions and is involved in plasticity and excitotoxicity. GABAergic neurochemistry underlies inhibition and predicts impaired psychophysical function in diabetes. It has also been associated with cognitive decline in people with diabetes. Still, the relation between metabolic homeostasis and neurotransmission remains elusive.Two 3T proton MR spectroscopy studies were independently conducted in the occipital cortex to provide insight into inhibitory/excitatory homeostasis (GABA/Glutamate) and to evaluate the impact of chronic metabolic control on the levels and regulation (as assessed by regression slopes) of the two main neurotransmitters of the CNS in type 2 diabetes (T2DM) and type 1 diabetes (T1DM).Compared to controls, participants with T2DM showed significantly lower Glutamate, and also GABA. Nevertheless, higher levels of GABA/Glx (Glutamate+Glutamine), and lower levels of Glutamate were associated with poor metabolic control in participants with T2DM. Importantly, the relationship between GABA/Glx and HbA1c found in T2DM supports a relationship between inhibitory/excitatory balance and metabolic control. Interestingly, this neurometabolic profile was undetected in T1DM. In this condition we found strong evidence for alterations in MRS surrogate measures of neuroinflammation (myo-Inositol), positively related to chronic metabolic control.Our results suggest a role for Glutamate as a global marker of T2DM and a sensitive marker of glycemic status. GABA/Glx may provide a signature of cortical metabolic state in poorly controlled patients as assessed by HbA1c levels, which indicate long-term blood Glucose control. These findings are consistent with an interplay between abnormal neurotransmission and metabolic control in particular in type 2 diabetes thereby revealing dissimilar contributions to the pathophysiology of neural dysfunction in both types of diabetes.

Regional Myo-Inositol, Creatine, and Choline Levels Are Higher at Older Age and Scale Negatively with Visuospatial Working Memory: A Cross-Sectional Proton MR Spectroscopy Study at 7 Tesla on Normal Cognitive Ageing

Proton MR spectroscopy (1H-MRS) has been used to assess regional neurochemical brain changes during normal ageing, but results have varied. Exploiting the increased sensitivity at ultra-high field, we performed 1H-MRS in 60 healthy human volunteers to asses age-related differences in metabolite levels and their relation to cognitive ageing. Sex was balanced, and participants were assigned to a younger, middle, and older group according to their age, ranging from 18 to 79 years. They underwent 7T 1H-MRS of the ACC, DLPFC, hippocampus, and thalamus and performed a visuospatial working memory task outside the scanner. A multivariate ANCOVA revealed a significant overall effect of age group on metabolite levels in all regions. Higher levels in the middle than the younger group were observed for myo-inositol (mIns) in DLPFC and hippocampus and total choline (tCho) in ACC. Higher levels in the older than the younger group were observed for mIns in hippocampus and thalamus, total creatine (tCr) and tCho in ACC and hippocampus; lower levels of glutamate (Glu) were observed in DLPFC. Higher levels in the older than the middle group were observed for mIns in hippocampus, tCr in ACC and hippocampus, tCho in hippocampus, and total N-acetyl aspartate (tNAA) in hippocampus. Working memory performance correlated negatively with tCr and tCho levels in ACC and mIns levels in hippocampus and thalamus, but not with tNAA or glutamate levels. As NAA and Glu are commonly regarded to reflect neuronal health and function and concentrations of mIns, tCr, and tCho are higher in glia than neurons, the findings of this study suggest a potential in vivo connection between cognitive ageing and higher regional levels of glia-related metabolites.SIGNIFICANCE STATEMENT Neurochemical ageing is an integral component of age-related cognitive decline. Proton MR spectroscopy (1H-MRS) studies of in vivo neurochemical changes across the lifespan have, however, yielded inconclusive results. 1H-MRS at ultra-high field strength can potentially improve the consistency of findings. Using 7T 1H-MRS, we assessed levels of mIns, tCr, and tCho (glia-related metabolites) and tNAA and Glu (neuron-related metabolites) in ACC, DLPFC, hippocampus, and thalamus. We found higher levels of glia-related metabolites in all brain regions in older individuals. Working memory performance correlated negatively with regional levels of glia-related metabolites. This study is the first to investigate normal ageing in these brain regions using 7T 1H-MRS and findings indicate that glia-related metabolites could be valuable in cognitive ageing studies.

Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy in Neonatal Hypoxic-Ischemic Encephalopathy: A review article

Background: Hypoxic Ischemic Encephalopathy is a subcategory of neonatal encephalopathy defined as a heterogeneous, clinically distinct syndrome characterized by disturbed neurological function, abnormal muscle tone and respiratory problems in the neonatal period in term infant, presented by a decreased level of consciousness, convulsions, decreased alertness, and often accompanied by difficulty with initiating and maintaining respiration. MRI plays an increasing important role for imaging the neonatal brain and follow up of neonates with HII. MR spectroscopy allows immediate analyses of the metabolites in the neonatal brain and also serves important role in assessment of neurological outcome and prognosis. The utility of proton MR spectroscopy could detect brain ischemic injuries in neonates with HII earlier than T2- or T1- weighted MR sequences. Diffusion-weighted imaging has the highest sensitivity for early detection of brain injury in neonates with HII. Findings seen at diffusion-weighted imaging mostly peak at 3–5 days after the insult of brain injury and then gradually normalize. Conclusions: MR spectroscopy is an accurate, sensitive and non-invasive method for early detection of perinatal ischemic brain injuries

Added-value of advanced magnetic resonance imaging to conventional morphologic analysis for the differentiation between benign and malignant non-fatty soft-tissue tumors.

To evaluate the added value of DWI, qualitative proton MR spectroscopy (H-MRS) and dynamic contrast-enhanced perfusion (DCE-P) to conventional MRI in differentiating benign and malignant non-fatty soft tissue tumors (NFSTT). From November 2009 to August 2017, 288 patients with NFSTT that underwent conventional and advanced MRI were prospectively evaluated. The study was approved by the local ethics committee. All patients signed an informed consent. A musculoskeletal (R1) and a general (R2) radiologist classified all tumors as benign, malignant, or indeterminate according to morphologic MRI features. Then, DWI, H-MRS, and DCE-P data of indeterminate tumors were analyzed by two additional radiologists (R3 and R4). Advanced techniques were considered individually and in combination for tumor benign-malignant differentiation using histology as the gold standard. There were 104 (36.1%) malignant and 184 (63.9%) benign tumors. Conventional MRI analysis classified 99 tumors for R1 and 135 for R2 as benign or malignant, an accuracy for the identification of malignancy of 87.9% for R1 and 83.7% for R2, respectively. There were 189 indeterminate tumors for R1. For these tumors, the combination of DWI and H-MRS yielded the best accuracy for malignancy identification (77.4%). DWI alone provided the best sensitivity (91.8%) while the combination of DCE-P, DWI, and H-MRS yielded the best specificity (100%). The reproducibility of the advanced imaging parameters was considered good to excellent (Kappa and ICC > 0.86). An advanced MRI evidence-based evaluation algorithm was proposed allowing to characterize 28.1 to 30.1% of indeterminate non-myxoid tumors. The prioritized use of advanced MRI techniques allowed to decrease by about 30% the number of non-myxoid NFSTT deemed indeterminate after conventional MRI analysis alone. • When morphological characterization of non-fatty soft tissue tumors is possible, the diagnostic performance is high and there is no need for advanced imaging techniques. • Following morphologic analysis, advanced MRI techniques reduced by about 30% the number of non-myxoid indeterminate tumors. • DWI is the keystone of advanced imaging techniques yielding the best sensitivity (91.8%). Optimal specificity (> 90%) is obtained by a combination of advanced techniques.

Feed-forward neural networks using cerebral MR spectroscopy and DTI might predict neurodevelopmental outcome in preterm neonates

ObjectivesWe aimed to evaluate the ability of feed-forward neural networks (fNNs) to predict the neurodevelopmental outcome (NDO) of very preterm neonates (VPIs) at 12 months corrected age by using biomarkers of cerebral MR proton spectroscopy (1H-MRS) and diffusion tensor imaging (DTI) at term-equivalent age (TEA).MethodsIn this prospective study, 300 VPIs born before 32 gestational weeks received an MRI scan at TEA between September 2013 and December 2017. Due to missing or poor-quality spectroscopy data and missing neurodevelopmental tests, 173 VPIs were excluded. Data sets consisting of 103 and 115 VPIs were considered for prediction of motor and cognitive developmental delay, respectively. Five metabolite ratios and two DTI characteristics in six different areas of the brain were evaluated. A feature selection algorithm was developed for receiving a subset of characteristics prevalent for the VPIs with a developmental delay. Finally, the predictors were constructed employing multiple fNNs and fourfold cross-validation.ResultsBy employing the constructed fNN predictors, we were able to predict cognitive delays of VPIs with 85.7% sensitivity, 100% specificity, 100% positive predictive value (PPV) and 99.1% negative predictive value (NPV). For the prediction of motor delay, we achieved a sensitivity of 76.9%, a specificity of 98.9%, a PPV of 90.9% and an NPV of 96.7%.ConclusionFNNs might be able to predict motor and cognitive development of VPIs at 12 months corrected age when employing biomarkers of cerebral 1H-MRS and DTI quantified at TEA.Key Points• A feed-forward neuronal network is a promising tool for outcome prediction in premature infants.• Cerebral proton magnetic resonance spectroscopy and diffusion tensor imaging can be used for the construction of early prognostic biomarkers.• Premature infants that would most benefit from early intervention services can be spotted at the time of optimal neuroplasticity.

Role of Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy in the diagnosis of Neonatal Hypoxic-Ischemic Injury

Background: Hypoxic Ischemic Encephalopathy is defined as a heterogeneous, clinically defined syndrome characterized by disturbed neurologic function in the earliest days of life in a neonate. Proton MR spectroscopy could reveal brain ischemic injuries in asphyxiated neonates earlier than T1- or T2-weighted MR imaging. MR spectroscopy and MR imaging is very important for the diagnosis of hypoxic-ischemic injury. Patients and Methods: A cross-sectional study. From December 2018 to December 2019, 50 full-term neonates were admitted to Neonatal Care Unit (NCU) in Sohag University Hospital with signs of HIE and referred to the Radio Diagnosis Department for brain imaging. MR imaging studies were performed using MRI system 1.5 tesla Achieva, Philips superconductive MRI system. Our MRI sequences 1. Axial T1WI. 2. Axial T2WI. 3. Axial FLAIR. 4. Axial DWI. 5. proton MR spectroscopyResults: The study included 50 neonates; 7 of them had normal MRI findings. The other 43 neonates showed different patterns of injury; 24 neonates showed a central pattern of injury,11 neonates show peripheral patterns of injury, While the other 8 neonates had shown both central and peripheral patterns of brain injury. Only 45 of examined neonates shows abnormal lactate peak. The sensitivity of MRS is 100%. However, the specificity is low 70 %, the overall accuracy is 60 %. Conclusion: MR spectroscopy is an accurate, sensitive and non-invasive method for early detection of perinatal ischemic brain injuries

In Vivo 1 H MR Spectroscopy of Biliary Components of Human Gallbladder at 7T.

BackgroundPrevious in vivo proton MR spectroscopy (MRS) studies have demonstrated the possibility of quantifying amide groups of conjugated bile acids (NHCBA), olefinic lipids and cholesterol (OLC), choline‐containing phospholipids (CCPLs), taurine and glycine conjugated bile acids (TCBA, GCBA), methylene group of lipids (ML), and methyl groups of bile acids, lipids, and cholesterol (BALC1.0, BALC0.9, and TBAC) in the gallbladder, which may be useful for the study of cholestatic diseases and cholangiopathies. However, these studies were performed at 1.5T and 3T, and higher magnetic fields may offer improved spectral resolution and signal intensity.PurposeTo develop a method for gallbladder MRS at 7T.Study TypeRetrospective, technical development.PopulationTen healthy subjects (five males and five females), two patients with primary biliary cholangitis (PBC) (one male and one female), and one patient with primary sclerosing cholangitis (PSC) (female).Field Strength/SequenceFree‐breathing single‐voxel MRS with a modified stimulated echo acquisition mode (STEAM) sequence at 7T.AssessmentPostprocessing was based on the T2 relaxation of water in the gallbladder and in the liver. Concentrations of biliary components were calculated using water signal. All data were corrected for T2 relaxation times measured in healthy subjects.Statistical TestsThe range of T2 relaxation time and concentration per bile component, and the resulting mean and standard deviation, were calculated.ResultsThe concentrations of gallbladder components in healthy subjects were: NHCBA: 93 ± 66 mM, OLC: 154 ± 124 mM, CCPL: 42 ± 17 mM, TCBA: 48 ± 35 mM, GCBA: 67 ± 32 mM, ML: 740 ± 391 mM, BALC1.0: 175 ± 92 mM, BALC0.9: 260 ± 138 mM, and TBAC: 153 ± 90 mM. Mean concentrations of all bile components were found to be lower in patients.Data ConclusionThis work provides a protocol for designing future MRS investigations of the bile system in vivo.Evidence Level2Technical Efficacy Stage1

Effects of effective stereotactic radiosurgery for brain metastases on the adjacent brain parenchyma

BackgroundTo evaluate whether functional and metabolic MRI can detect radiation-induced alterations in the adjacent areas after effective stereotactic radiosurgery (SRS) for brain metastases. If confirmed, these techniques may be suited for monitoring the timely stratification of patients for neuroprotective treatments after irradiation.MethodsInclusion criteria were complete response, partial response, or stable disease on routine follow-up MR-scans. Multiparametric 3T-MRI was performed with diffusion-weighted imaging, dynamic susceptibility perfusion-weighted imaging, and two-dimensional proton MR-spectroscopy. Parameters were measured in the SRS-treated target and in the adjacent parenchyma up to both 0.75 cm and 1.5 cm from the target border.ResultsNineteen lesions in sixteen consecutive patients met the inclusion criteria. The median follow-up time was 39 months (range, 10–142) with 41 multiparametric MR-examinations in total. We found low values of N-acetyl-aspartate up to 1.5 cm from the target borders of SRS (P = 0.043) associated with high values of choline (P = 0.004) at the end of the observation period. Lactate levels in the adjacent tissue declined over time, whereas continuously high apparent-diffusion-coefficient values were noted (P < 0.001).ConclusionMultiparametric MRI can depict radiobiological effects and their time course at a distance from the effectively treated site after SRS for brain metastases, even if conventional MRI findings are inconspicuous.

Neural Signatures of Memory Encoding in Schizophrenia Are Modulated by Antipsychotic Treatment

There is no pharmacological treatment to remediate cognitive impairment in schizophrenia (SZ). It is imperative to characterize underlying pathologies of memory processing in order to effectively develop new treatments. In this longitudinal study, we combined functional magnetic resonance imaging during a memory encoding task with proton MR spectroscopy to measure hippocampal glutamate + glutamine (Glx). Seventeen SZ were scanned while unmedicated and after 6 weeks of treatment with risperidone and compared to a group of matched healthy controls (HC) scanned 6 weeks apart. Unmedicated patients showed reduced blood oxygen level dependent (BOLD) response in several regions, including the hippocampus, and greater BOLD response in regions of the default mode network (DMN) during correct memory encoding. Post hoc contrasts from significant group by time interactions indicated reduced hippocampal BOLD response at baseline with subsequent increase following treatment. Hippocampal Glx was not different between groups at baseline, but at week 6, hippocampal Glx was significantly lower in SZ compared to HC. Finally, in unmedicated SZ, higher hippocampal Glx predicted less deactivation of the BOLD response in regions of the DMN. Using 2 brain imaging modalities allowed us to concurrently investigate different mechanisms involved in memory encoding dysfunction in SZ. Hippocampal pathology during memory encoding stems from decreased hippocampal recruitment and faulty deactivation of the DMN, and hippocampal recruitment during encoding can be modulated by antipsychotic treatment. High Glx in unmedicated patients predicted less deactivation of the DMN; these results suggest a mechanism by which faulty DMN deactivation, a hallmark of pathological findings in SZ, is achieved.

Upper and Lower Extremities in Duchenne Muscular Dystrophy Evaluated with Quantitative MRI and Proton MR Spectroscopy in a Multicenter Cohort.

Background Upper extremity MRI and proton MR spectroscopy are increasingly considered to be outcome measures in Duchenne muscular dystrophy (DMD) clinical trials. Purpose To demonstrate the feasibility of acquiring upper extremity MRI and proton (1H) MR spectroscopy measures of T2 and fat fraction in a large, multicenter cohort (ImagingDMD) of ambulatory and nonambulatory individuals with DMD; compare upper and lower extremity muscles by using MRI and 1H MR spectroscopy; and correlate upper extremity MRI and 1H MR spectroscopy measures to function. Materials and Methods In this prospective cross-sectional study, MRI and 1H MR spectroscopy and functional assessment data were acquired from participants with DMD and unaffected control participants at three centers (from January 28, 2016, to April 24, 2018). T2 maps of the shoulder, upper arm, forearm, thigh, and calf were generated from a spin-echo sequence (repetition time msec/echo time msec, 3000/20-320). Fat fraction maps were generated from chemical shift-encoded imaging (eight echo times). Fat fraction and 1H2O T2 in the deltoid and biceps brachii were measured from single-voxel 1H MR spectroscopy (9000/11-243). Groups were compared by using Mann-Whitney test, and relationships between MRI and 1H MR spectroscopy and arm function were assessed by using Spearman correlation. Results This study evaluated 119 male participants with DMD (mean age, 12 years ± 3 [standard deviation]) and 38 unaffected male control participants (mean age, 12 years ± 3). Deltoid and biceps brachii muscles were different in participants with DMD versus control participants in all age groups by using quantitative T2 MRI (P < .001) and 1H MR spectroscopy fat fraction (P < .05). The deltoid, biceps brachii, and triceps brachii were affected to the same extent (P > .05) as the soleus and medial gastrocnemius. Negative correlations were observed between arm function and MRI (T2: range among muscles, ρ = -0.53 to -0.73 [P < .01]; fat fraction, ρ = -0.49 to -0.70 [P < .01]) and 1H MR spectroscopy fat fraction (ρ = -0.64 to -0.71; P < .01). Conclusion This multicenter study demonstrated early and progressive involvement of upper extremity muscles in Duchenne muscular dystrophy (DMD) and showed the feasibility of MRI and 1H MR spectroscopy to track disease progression over a wide range of ages in participants with DMD. © RSNA, 2020 Online supplemental material is available for this article.

In vivo biochemical investigation of spermatogenic status: 1H-MR spectroscopy of testes with nonobstructive azoospermia.

To evaluate the biochemical milieu in testes with nonobstructive azoospermia (NOA) by using proton MR spectroscopy (1H-MRS) in detecting differences in testicular metabolites between histological stages of NOA and in assessing the possible presence of spermatozoa before microdissection testicular sperm extraction (mTESE). Forty-nine NOA men and fifty age-matched controls were included in this prospective study. A single-voxel point-resolved spectroscopy sequence with TR/TE (2000/25ms) was used. NOA testes were classified using the higher Johnsen score (hJS) (group 1, hJS ≥ 8; and group 2, hJS < 8). Nonparametric statistical tests were used to assess differences in normalized metabolite concentrations, defined as ratios of the metabolite concentrations versus creatine concentration between (a) NOA and controls, (b) NOA groups, and (c) NOA with positive and negative sperm retrieval. Normalized concentrations of total choline (median 0.396 vs 1.09mmol/kg, p = 0.002), myo-inositol (median 1.985 vs 3.19mmol/kg, p = 0.002), and total lipids and macromolecules (TLM) resonating at 0.9ppm (median 0.962 vs 2.43mmol/kg, p = 0.024), 1.3ppm (median 4.88 vs 10.7mmol/kg, p = 0.043), and 2.0ppm (median 2.33 vs 5.96mmol/kg, p = 0.007) were reduced in NOA testes compared with controls. Decreased concentrations of TLM 2.0 (median 3.755 vs 0.436mmol/kg, p = 0.043) were found in group 2 compared with group 1. Increased normalized concentrations of glutamate were observed in NOA testes with failed sperm retrieval (median 0.321 vs 0.000mmol/kg, p = 0.028). 1H-MRS provides metabolic information about the testis in NOA patients and assesses spermatogenic status before mTESE. • NOA testes differed from age-matched controls, in terms of reduced normalized concentrations of tChol, mI, and lipids. • TLM 2.0 peaks were found useful in the identification of NOA testes with the presence of foci of advanced spermatogenesis up to the haploid gamete stage. • Glu proved a reliable metabolic signature of spermatogenesis in NOA population by assessing the possible presence of sperm after mTESE.

Clinical relevance of total choline (tCho) quantification in suspicious lesions on multiparametric breast MRI

PurposeTo assess the additional value of quantitative tCho evaluation to diagnose malignancy and lymph node metastases in suspicious lesions on multiparametric breast MRI (mpMRI, BI-RADS 4, and BI-RADS 5).MethodsOne hundred twenty-one patients that demonstrated suspicious multiparametric breast MRI lesions using DCE, T2w, and diffusion-weighted (DW) images were prospectively enrolled in this IRB-approved study. All underwent single-voxel proton MR spectroscopy (1H-MRS, point-resolved spectroscopy sequence, TR 2000 ms, TE 272 ms) with and without water suppression. The total choline (tCho) amplitude was measured and normalized to millimoles/liter according to established methodology by two independent readers (R1, R2). ROC-analysis was employed to predict malignancy and lymph node status by tCho results.ResultsOne hundred three patients with 74 malignant and 29 benign lesions had full 1H-MRS data. The area under the ROC curve (AUC) for prediction of malignancy was 0.816 (R1) and 0.809 (R2). A cutoff of 0.8 mmol/l tCho could diagnose malignancy with a sensitivity of > 95%. For prediction of lymph node metastases, tCho measurements achieved an AUC of 0.760 (R1) and 0.788 (R2). At tCho levels < 2.4 mmol/l, no metastatic lymph nodes were found.ConclusionQuantitative tCho evaluation from 1H-MRS allowed diagnose malignancy and lymph node status in breast lesions suspicious on multiparametric breast MRI. tCho therefore demonstrated the potential to downgrade suspicious mpMRI lesions and stratify the risk of lymph node metastases for improved patient management.Key Points• Quantitative tCho evaluation can distinguish benign from malignant breast lesions suspicious after multiparametric MRI assessment.• Quantitative tCho levels are associated with lymph node status in breast cancer.• Quantitative tCho levels are higher in hormonal receptor positive compared to hormonal receptor negative lesions.

Proton MR spectroscopy in characterization of focal bone lesions of peripheral skeleton

BackgroundThe aim of our study was to determine the value of single-voxel proton MR spectroscopy (1HMRS) in distinguishing benign from malignant focal bone lesions in the peripheral skeleton. MRI and 1HMRS was performed in 50 focal lesions (> 1 cm size) detected on radiographs of peripheral skeleton.1HMRS was performed at 1.5 T with TE of 144 ms with automatic shimming and water suppression. Qualitative analysis for a discrete choline peak at 3.2 ppm was done. Significance of the presence of choline peak on 1HMRS in distinguishing benign from malignant lesions was calculated using histopathology as a gold standard. Chi-square test was used and p value < 0.05 was considered significant.ResultsForty-one benign and 9 malignant lesions were confirmed by histopathological results. Amongst malignant lesions, choline peak was positive in all but 1 case of low-grade lymphoma. MR spectra of 11 benign lesions showed the presence of choline peak. All 7 benign giant cell tumors (GCT) were positive for choline peak. The sensitivity, specificity, PPV, NPV of proton MR spectroscopy in differentiating benign from malignant lesions were 87.5%,71%,38.8%, and 96.4% respectively. p value was significant (< 0.05).Conclusion1HMRS in focal bone lesions can help in the differentiation of malignant from benign musculoskeletal tumors. Although some benign lesions may show false-positive result, absence of choline peak is a reliable reassurance against malignancy. GCT is an exception amongst benign bone tumors as it consistently shows the presence of choline peak on 1HMRS.

Value of magnetic resonance spectroscopy in assessment of adnexal lesions

BackgroundThe purpose of this study is to investigate the role of proton MR spectroscopy (1H-MRS) in the characterization and diagnosis of ovarian lesions.ResultsFrom October 2015 to October 2017, a total of 57 female patients (65 adnexal lesions; 8 cases were bilateral) were included. The examined lesions were classified according to their histopathological findings, (37 (57%) benign lesions, 4 (6%) borderline lesions, and 24 (37%) malignant lesions). The mean choline/creatinine (CHO/Cr) ratio was 1.29 ± 0.98 SD for malignant lesions, while the mean value in borderline lesions was 0.63 ± 0.15 SD, and the mean value for the benign lesions was 0.65 ± 0.34. Therefore, the mean CHO/Cr ratio was much higher in malignant than in benign lesions, which was statistically significant (P ≤ 0.001) as well as between the borderline and invasive lesions (P = 0.05), but not between the benign and borderline lesions. The diagnostic performance of conventional MRI in diagnosing adnexal lesions was 100%, specificity was 76%, and accuracy was 86%. However, MRS individual diagnostic performances are the following: sensitivity 89%, specificity, and 100% with an accuracy of 95%.ConclusionMRS proved to be an accurate and efficient method for the analysis of adnexal lesions and in differentiation between benign and malignant tumors.

Comparison of dynamic brain metabolism during antegrade cerebral perfusion versus deep hypothermic circulatory arrest using proton magnetic resonance spectroscopy

Comparison of dynamic brain metabolism during antegrade cerebral perfusion versus deep hypothermic circulatory arrest using proton magnetic resonance spectroscopy

Placebo-controlled randomised trial with liraglutide on magnetic resonance endpoints in individuals with type 2 diabetes: a pre-specified secondary study on ectopic fat accumulation

Aims/hypothesisThe aim of this work was to assess the effect of liraglutide on ectopic fat accumulation in individuals with type 2 diabetes mellitus.MethodsThis study is a pre-specified subanalysis of the MAGNetic resonance Assessment of VICTOza efficacy in the Regression of cardiovascular dysfunction In type 2 diAbetes mellitus (MAGNA VICTORIA) study, with primary endpoints being the effects of liraglutide on left ventricular diastolic and systolic function. The MAGNA VICTORIA study was a single-centre, parallel-group trial in 50 individuals with type 2 diabetes mellitus (BMI >25 kg/m2) who were randomly assigned (1:1, stratified for sex and insulin use) to receive liraglutide 1.8 mg once daily or placebo for 26 weeks, added to standard care. Participants, study personnel and outcome assessors were blinded to treatment allocation. The secondary endpoints of visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (SAT) and epicardial fat were measured with MRI. Hepatic triacylglycerol content (HTGC) and myocardial triacylglycerol content (MTGC) were quantified with proton MR spectroscopy. Between-group differences (change from baseline) were tested for significance using ANCOVA. Mean differences with 95% CIs were reported.ResultsThe trial was completed in 2016. Twenty-four participants were randomised to receive liraglutide and 26 to receive placebo. One patient in the liraglutide group withdrew consent before having received the study drug and was not included in the intention-to-treat analysis. Liraglutide (n = 23) vs placebo (n = 26) significantly reduced body weight (liraglutide 98.4 ± 13.8 kg to 94.3 ± 14.9 kg; placebo 94.5 ± 13.1 kg to 93.9 ± 13.2 kg; estimated treatment effect −4.5 [95% CI −6.4, −2.6] kg). HbA1c declined in both groups without a significant treatment effect of liraglutide vs placebo (liraglutide 66.7 ± 11.5 mmol/mol to 55.0 ± 13.2 mmol/mol [8.4 ± 1.1% to 7.3 ± 1.2%]; placebo 64.7 ± 10.2 mmol/mol to 56.9 ± 6.9 mmol/mol [8.2 ± 1.0% to 7.5 ± 0.7%]; estimated treatment effect −2.9 [95% CI −8.1, 2.3] mmol/mol or −0.3 [95% CI −0.8, 0.2]%). VAT did not change significantly between groups (liraglutide 207 ± 87 cm2 to 203 ± 88 cm2; placebo 204 ± 63 cm2 to 200 ± 55 cm2; estimated treatment effect −7 [95% CI −24, 10] cm2), while SAT was reduced by a significantly greater extent with liraglutide than with placebo (liraglutide 361 ± 142 cm2 to 339 ± 131 cm2; placebo 329 ± 107 cm2 to 333 ± 125 cm2; estimated treatment effect −29 [95% CI −51, −8] cm2). Epicardial fat did not change significantly between groups (liraglutide 8.9 ± 4.3 cm2 to 9.1 ± 4.7 cm2; placebo 9.6 ± 4.1 cm2 to 9.6 ± 4.6 cm2; estimated treatment effect 0.2 [95% CI −1.5, 1.8] cm2). Change in HTGC was not different between groups (liraglutide 18.1 ± 11.2% to 12.0 ± 7.7%; placebo 18.4 ± 9.4% to 14.7 ± 10.0%; estimated treatment effect −2.1 [95% CI −5.3, 1.0]%). MTGC was not different after treatment with liraglutide (1.5 ± 0.6% to 1.2 ± 0.6%) vs placebo (1.3 ± 0.5% to 1.2 ± 0.6%), with an estimated treatment effect of −0.1 (95% CI −0.4, 0.2)%. There were no adjudicated serious adverse events.Conclusions/interpretationCompared with placebo, liraglutide-treated participants lost significantly more body weight. Liraglutide primarily reduced subcutaneous fat but not visceral, hepatic, myocardial or epicardial fat. Future larger studies are needed to confirm the results of this secondary endpoint study.Trial registrationClinicalTrials.gov NCT01761318.FundingThis study was funded by Novo Nordisk A/S (Bagsvaerd, Denmark).