Single-voxel 1H Magnetic Resonance Spectroscopy Research Articles

Single Voxel ¹H-MR Spectroscopy in the Human Spinal Cord at 3T -Preliminary Results

Purpose: ¹H-Magnetic Resonance Spectroscopy is a non-invasive technique that provides information on tissue metabolism and biochemistry. Because of technical difficulties, this method is rarely used in the spinal cord examination. The main goal of this study was to develop a routine protocol for MRS of intramedullary lesions. Material and methods: ¹H-MRS protocol was set on a group of healthy volunteers. 48 spectra were acquired in total. 30 of them were acquired in cervical spinal cord and the remaining (18 spectra) were acquired in the thoracic spinal cord. Results: In ¹H-MRS of the spinal cord one of the most important problem is small voxel size. Mean voxel size in this study was 7x9x29 mm - what is much smaller than in the brain examinations finally, almost 60% of spectra were of acceptable quality in volunteer examinations, what enabled the following patients’ examinations. Conclusions: Challenges of spinal cord spectroscopy were discussed and the ability of providing additional diagnostic information was proved.

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.

P6203Intramyocellular lipid saturation as a new metabolic biomarker

Abstract Background Endurance trained athletic healthy volunteers (Athl-HV) and type 2 diabetes patients (T2D) have higher levels of lipids in their skeletal myocytes compared to healthy controls. Despite apparently similar metabolic storage, they are at opposite ends of insulin sensitivity and cardio-metabolic risk. Purpose We investigated if the degree of saturation of the IntraMyoCellular Lipids (IMCL) will differentiate Athl-HV from T2D; and explored if an exercise intervention will induce changes in the IMCL saturation. Methods Male, age matched Athl-HV and T2D were enrolled (n=25/group). Athl-HV had ≥5 years endurance training, T2D were sedentary. Subjects were studied at baseline and after an exercise intervention (4 week deconditioning in Athl-HV and supervised bike training at ≥65% of peakVO2, 5 hours/week x 8 weeks in T2D). All subjects underwent cardio-pulmonary exercise testing (CPET), blood sampling for insulin sensitivity (QUICKI*) and single voxel 1H-magnetic resonance spectroscopy (1H-MRS) of the right vastus lateralis. 1H-MRS was acquired on 3T Philips Achieva with a 16-channel coil, point-resolved spectroscopy, variable pulse power and optimized relaxation delay water suppression and analysed in LCModel. We derived fractional lipid mass (fLM) and fractions of saturated (fSL) and unsaturated (fUL) lipids. Data were analysed by t tests, shown as mean±SEM, statistical significance p&lt;0.05. Results CPET and insulin sensitivity are presented in Table 1. T2D had higher fLM in the skeletal muscle compared to Athl-HV, at baseline (p=0.003) and after the exercise intervention (p=0.009), Figure 1A. At baseline, T2D had a different phenotype with a lower fSL and higher fUL compared to Athl-HV (82±3 vs 88±1% and 18±3 vs 12±1%, p=0.02 for both). Whilst deconditioning did not attract any significant changes in either fSL or fUL in Athl-HV (88±1 to 86±1% and 12±1 to 14±1, p=0.2), in contrast, with exercise training T2D significantly increased fSL (82±3 to 88±1%) and decreased their fUL (18±3 to 12±1%) (both p=0.01). Figure 1B and 1C. CPET and insulin sensitivity results Athl-HV Baseline Athl-HV Deconditioning p value T2D Baseline T2D After Training p value VO2 peak, (mL/kg/min) 45.0±0.9† 41.7±0.9‡ &lt;0.0001 23.6±0.6† 30.3±0.6‡ &lt;0.0001 QUICKI* 0.346±0.002† 0.343±0.003‡ 0.2 0.308±0.004† 0.317±0.004‡ 0.02 *QUICKI: Quantitative Insulin Sensitivity Check Index; †Athl-HV vs T2D at baseline p≤0.001, ‡Athl-HV vs T2D after exercise intervention p≤0.001. Figure 1 Conclusion We demonstrate for the first time, in vivo, significant differences in the IMCL amount and saturation between Athl-HV and T2D. IMCL saturation was changed by exercise training in T2D to mirror the phenotype seen in Athl-HV uncovering a new, independent biomarker of improved cardio-metabolic health. Acknowledgement/Funding British Heart Foundation Project Grant no. PG/15/88/31780

Is 1H-MR spectroscopy useful as a diagnostic aid in MSA-C?

BackgroundMultiple system atrophy (MSA) is a sporadic adult-onset neurodegenerative disease with a cerebellar subtype where ataxic symptoms predominate (MSA-C) associated with autonomic dysfunction and a grave prognosis. The purpose of this analysis was to identify if cerebellar volumetry and MR spectroscopy obtained as part of routine clinical work up of patients with sporadic ataxia differentiates patients with multiple system atrophy- cerebellar type (MSA-C) from those with sporadic adult-onset ataxia of unknown etiology (SAOA) who’s condition follows a more benign course.MethodsRetrospective comparison was undertaken of 20 clinically probable or possible MSA-C patients, 20 age and sex matched patients with SAOA and 20 healthy control subjects. Single voxel 1H-MR spectroscopy of the cerebellar hemisphere and vermis and volumetric analysis of the cerebellum and brainstem were undertaken on baseline scans, comparing all groups.ResultsThere was significant reduction in NAA/Cr levels in patients with MSA-C when compared to those with ISA (p = 0.005) and healthy controls (p < 0.001) in both the hemisphere and vermis. Brainstem volume was significantly reduced in MSA-C patients compared to SAOA patients (p < 0.001) and healthy controls (p < 0.001). There was no difference in cerebellar volume between MSA-C patients and SAOA patients.ConclusionThis paper demonstrates that at presentation, MSA-C patients have a significant reduction of NAA/Cr in the cerebellum and significant decrease in brainstem volume when compared to SAOA and healthy controls. This is the first study to sucessfully show clinical utility of MR spectroscopy of the cerebellum for differentiating MSA-C from patients with SAOA.

Effects of Alcohol Cues on MRS Glutamate Levels in the Anterior Cingulate

Growing evidence suggests that glutamate neurotransmission plays a critical role in alcohol addiction. Cue-induced change of glutamate has been observed in animal studies but never been investigated in humans. This work investigates cue-induced change in forebrain glutamate in individuals with alcohol use disorder (AUD). A total of 35 subjects (17 individuals with AUD and 18 healthy controls) participated in this study. The glutamate concentration was measured with single-voxel 1H-MR spectroscopy at the dorsal anterior cingulate. Two MRS sessions were performed in succession, the first to establish basal glutamate levels and the second to measure the change in response to alcohol cues. The changes in glutamate were quantified for both AUD subjects and controls. A mixed model ANOVA and t-tests were performed for statistical analysis. ANOVA revealed a main effect of cue-induced decrease of glutamate level in the anterior cingulate cortex (ACC). A significant interaction revealed that only AUD subjects showed significant decrease of glutamate in the ACC. There were no significant group differences in the level of basal glutamate. However, a negative correlation was found between the basal glutamate level and the number of drinking days in the past 2 weeks for the AUD subjects. Collectively, our results indicate that glutamate in key areas of the forebrain reward circuit is modulated by alcohol cues in early alcohol dependence.

In Vivo 1H Magnetic Resonance Spectroscopy.

In vivo Magnetic Resonance Spectroscopy (MRS) allows the non-invasive detection and quantification of a number of metabolites from localized volumes within a living organism. MRS localization techniques can be divided into two main groups, single voxel and multi-voxel. Single voxel techniques provide the metabolic profile from a specific small volume, whereas multi-voxel techniques are used to obtain the spatial distribution of metabolites throughout a large volume subdivided into small contiguous voxels. This chapter describes standard protocols for the acquisition and processing of in vivo single voxel1H MRS data from the rodent brain.

Evaluation of the Braak staging of brain pathology with 1 H-MRS in patients with Parkinson’s disease

The Braak staging of Parkinson's disease (PD) pathology is usually based on the brain autopsy, which has not been confirmed in living patients of PD. In this study, we investigated the metabolites of medulla oblongata, substantia nigra (SN), putamen, and motor cortex by measuring N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine (Cr) in 22 patients of PD and 15 age-matched healthy controls, using single-voxel 1H-magnetic resonance spectroscopy (1H-MRS). The results showed that NAA/Cr in SN was lower in PD group than that in control group (p=0.006), however, there was no difference for NAA/Cr and Cho/Cr between PD group and control group in other regions. In SN, NAA/Cr was negatively correlated with Unified Parkinson's Disease Rating Scale (UPDRS) (r=-0.743, p=0.002) and Hoehn-Yahr staging (r=-0.714, p=0.003), while Cho/Cr was positively correlated with UPDRS (r=0.850, p<0.001) and Hoehn-Yahr staging (r=0.647, p=0.009). In PD group, the variance of NAA/Cr in SN was significantly larger than that in other regions (p=0.005), but there was no difference for the variance of Cho/Cr among regions of interesting (ROIs) (p=0.267). These results indicate that SN is the most seriously injured region in PD, and the metabolites in SN measured by 1H-MRS is correlated with the severity of PD. However, the Braak staging of PD pathology is not validated by 1H-MRS.

Application of Single Voxel 1H Magnetic Resonance Spectroscopy in Hepatic Benign and Malignant Lesions

BackgroundTo quantify the metabolite changes in hepatic tumors by single-voxel 1H magnetic resonance spectroscopy (MRS) at 3.0 T and explore the application value of 1HMRS in the diagnosis of hepatic benign and malignant lesions.Material/MethodsA total of 45 patients (55 lesions) diagnosed with hepatic lesions by ultrasound and/or computer topography (CT) from November 2006 to March 2007 were included in this study. All patients underwent 3D-dynamic enhanced scan with liver acquisition with acceleration volume acquisition (LAVA) sequence and single-voxel 1HMRS imaging with PRESS (point-resolved spectroscopy) sequence. The metabolite concentrations such as choline (Cho) and lipids (Lip) were measured.ResultsThere was significant difference regarding the occurrence rate of the obvious elevated Cho peaks between benign and malignant tumors (7/27 vs. 21/28, p=0.000). There was statistical significant differences regarding the Cho/Lip ratios in hepatic benign (0.0686±0.0283, 95% CI: 0.0134–0.1245) and malignant (0.1266±0.1124, 95% CI: 0.0937–0.2203) lesions (p<0.05). When compared with the pathological results, the sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were 85.7% (24/28), 92.6% (25/27), 92.3% (24/26), 86.2% (25/29), and 89.1% (49/55) respectively for the MRI assessment, and 92.6% (26/28), 88.9% (24/27), 89.7 (26/29), 92.3 (24/26), and 90.9% (50/55) respectively for 1HMRS combined with MRI assessment.ConclusionsSingle Cho peaks or Lip peaks cannot be used for the diagnosis of hepatic benign and malignant lesions. Combined use of 1HMRS and MRI can greatly improve the application value of MRI assessment in the diagnosis of hepatic benign and malignant lesions with a higher sensitivity, negative predictive value, and overall accuracy.

Creatine, Glutamine plus Glutamate, and Macromolecules Are Decreased in the Central White Matter of Premature Neonates around Term.

Preterm birth represents a high risk of neurodevelopmental disabilities when associated with white-matter damage. Recent studies have reported cognitive deficits in children born preterm without brain injury on MRI at term-equivalent age. Understanding the microstructural and metabolic underpinnings of these deficits is essential for their early detection. Here, we used diffusion-weighted imaging and single-voxel 1H magnetic resonance spectroscopy (MRS) to compare brain maturation at term-equivalent age in premature neonates with no evidence of white matter injury on conventional MRI except diffuse excessive high-signal intensity, and normal term neonates. Thirty-two infants, 16 term neonates (mean post-conceptional age at scan: 39.8±1 weeks) and 16 premature neonates (mean gestational age at birth: 29.1±2 weeks, mean post-conceptional age at scan: 39.2±1 weeks) were investigated. The MRI/MRS protocol performed at 1.5T involved diffusion-weighted MRI and localized 1H-MRS with the Point RESolved Spectroscopy (PRESS) sequence. Preterm neonates showed significantly higher ADC values in the temporal white matter (P<0.05), the occipital white matter (P<0.005) and the thalamus (P<0.05). The proton spectrum of the centrum semiovale was characterized by significantly lower taurine/H2O and macromolecules/H2O ratios (P<0.05) at a TE of 30 ms, and reduced (creatine+phosphocreatine)/H2O and (glutamine+glutamate)/H2O ratios (P<0.05) at a TE of 135 ms in the preterm neonates than in full-term neonates. Our findings indicate that premature neonates with normal conventional MRI present a delay in brain maturation affecting the white matter and the thalamus. Their brain metabolic profile is characterized by lower levels of creatine, glutamine plus glutamate, and macromolecules in the centrum semiovale, a finding suggesting altered energy metabolism and protein synthesis.

Early brain magnetic resonance imaging can predict short and long-term outcomes after organophosphate poisoning in a rat model

IntroductionMagnetic resonance (MR) imaging is a sensitive modality for demonstrating in vivo alterations in brain structure and function after acute organophosphate (OP) poisoning. The goals of this study were to explore early imaging findings in organophosphate-poisoned animals, to assess the efficacy of centrally acting antidotes and to find whether early MR findings can predict post-poisoning cognitive dysfunction. MethodsSprague–Dawley rats were poisoned with the agricultural OP paraoxon and were treated with immediate atropine and obidoxime (ATOX) to reduce acute mortality caused by peripheral inhibition of acetylcholinesterase. Animals were randomly divided into three groups based on the protocol of centrally acting antidotal treatment: group 1 – no central antidotal treatment (n=10); group 2 – treated with midazolam (MID) at 30min after poisoning (n=9), group 3 – treated with a combination of MID and scopolamine (SCOP) at 30min after poisoning (n=9) and controls (n=6). Each animal had a brain MR examination 3 and 24h after poisoning. Each MR examination included the acquisition of a T2 map and a single-voxel 1H MR spectroscopy (localized on the thalami, to measure total creatine [Cr], N-acetyl-aspartate [NAA] and cholines [Cho] levels). Eleven days after poisoning each animal underwent a Morris water maze to assess hippocampal learning. Eighteen days after poisoning, animals were euthanized, and their brains were dissected, fixed and processed for histology. ResultsAll paraoxon poisoned animals developed generalized convulsions, starting within a few minutes following paraoxon injection. Brain edema was maximal on MR imaging 3h after poisoning. Both MID and MID+SCOP prevented most of the cortical edema, with equivalent efficacy. Brain metabolic dysfunction, manifested as decreased NAA/Cr, appeared in all poisoned animals as early as 3h after exposure (1.1±0.07 and 1.42±0.05 in ATOX and control groups, respectively) and remained lower compared to non-poisoned animals even 24h after poisoning. MID and MID+SCOP prevented much of the 3h NAA/Cr decrease (1.22±0.05 and 1.32±0.1, respectively). Significant correlations were found between imaging findings (brain edema and spectroscopic changes) and clinical outcomes (poor learning, weight loss and pathological score) with correlation coefficients of 0.4–0.75 (p<0.05). ConclusionsMR imaging is a sensitive modality to explore organophosphate-induced brain damage. Delayed treatment with midazolam with or without scopolamine provides only transient neuroprotection with some advantage in adding scopolamine. Early imaging findings were found to correlate with clinical consequences of organophosphate poisoning and could be potentially used in the future to predict long-term prognosis of poisoned casualties.

Cerebral lipid accumulation in Chanarin–Dorfman Syndrome

Chanarin–Dorfman Syndrome (CDS) is caused by a defect in the CGI-58/ABHD5 gene resulting in a deficiency of CGI-58 and in intracellular accumulation of triacylglycerol in skin and liver. Patients are mainly characterized by congenital ichthyosis, but the clinical phenotype is very heterogeneous. Distinct brain involvement has never been described.We present a clinical description of two patients with congenital ichthyosis. On suspicion of Sjögren–Larsson syndrome (SLS) single-voxel 1H-MR spectroscopy of the brain was performed and biochemical testing of fatty aldehyde dehydrogenase (FALDH) to establish this diagnosis gave normal results.Vacuolisation in a peripheral blood smear has led to the CDS suspicion. In both patients the diagnosis CDS was confirmed by ABHD5 mutation analysis. Interestingly, a clear lipid accumulation in the cerebral white matter, cortex and basal ganglia was demonstrated in both CDS-patients.These results demonstrate, for the first time, cerebral involvement in CDS and give new insights in the complex phenotype. Since the clinical implications of this abnormal cerebral lipid accumulation are still unknown, further studies are warranted.

Manifold Learning in MR spectroscopy using nonlinear dimensionality reduction and unsupervised clustering.

To investigate whether nonlinear dimensionality reduction improves unsupervised classification of (1) H MRS brain tumor data compared with a linear method. In vivo single-voxel (1) H magnetic resonance spectroscopy (55 patients) and (1) H magnetic resonance spectroscopy imaging (MRSI) (29 patients) data were acquired from histopathologically diagnosed gliomas. Data reduction using Laplacian eigenmaps (LE) or independent component analysis (ICA) was followed by k-means clustering or agglomerative hierarchical clustering (AHC) for unsupervised learning to assess tumor grade and for tissue type segmentation of MRSI data. An accuracy of 93% in classification of glioma grade II and grade IV, with 100% accuracy in distinguishing tumor and normal spectra, was obtained by LE with unsupervised clustering, but not with the combination of k-means and ICA. With (1) H MRSI data, LE provided a more linear distribution of data for cluster analysis and better cluster stability than ICA. LE combined with k-means or AHC provided 91% accuracy for classifying tumor grade and 100% accuracy for identifying normal tissue voxels. Color-coded visualization of normal brain, tumor core, and infiltration regions was achieved with LE combined with AHC. The LE method is promising for unsupervised clustering to separate brain and tumor tissue with automated color-coding for visualization of (1) H MRSI data after cluster analysis.

Prefrontal grey and white matter neurometabolite changes after atomoxetine and methylphenidate in children with attention deficit/hyperactivity disorder: A 1H magnetic resonance spectroscopy study

Attention deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral childhood disorder. Dysfunction of prefrontal neural circuits which are responsible for executive and attentional functions has been previously shown in ADHD. We investigated the neurometablite changes in areas included in dorsolateral prefrontal neural circuits after 2 months of long-acting methylphenidate or atomoxetine medication in children with ADHD who were responders to treatment. Twenty-one ADHD children were examined by single voxel 1H-magnetic resonance spectroscopy (MRS) before and after 2 months of medication with OROS methylphenidate (n=10) or atomoxetine (n=11). The spectra were taken from the dorsolateral prefrontal cortex (DLPFC, 8ml) and white matter behind the DLPFC (anterior semioval center, 7.5ml), bilaterally. NAA and NAA/Cr (N-acetylaspartate/creatine) decreased in the left DLPFC and Cho/Cr (choline/creatine) increased in the right DLPFC after atomoxetine medication. Glu+Gln and Glu+Gln/Cr (glutamate/glutamine) increased in the left white matter after methylphenidate medication. We hypothesize that atomoxetine could decrease hyperactivation of DLPFC neurons and methylphenidate could lead to increased activation of cortical glutamatergic projections with the consequences of increased tonic dopamine release in the mesocortical system.

Anterior cingulate cortex and cerebellar hemisphere neurometabolite changes in depression treatment: A 1H magnetic resonance spectroscopy study

We utilized single-voxel 1H magnetic resonance spectroscopy to determine biochemical abnormalities related to major depressive disorder (MDD) in the bilateral dorsolateral prefrontal cortex, anterior cingulate cortex (ACC), and cerebellar hemisphere before and after antidepressant treatment. Fifteen adult MDD patients and 15 age- and sex-matched healthy controls were involved. Magnetic resonance spectroscopy of the brain was conducted in all subjects at the beginning of the study and the depressed subjects were reassessed after 8 weeks of antidepressant treatment. At baseline, N-acetyl aspartate (NAA), total glutamine plus glutamate (Glx) and myo-inositol (MI) levels in the bilateral ACC were significantly lower in MDD patients than in controls (P < 0.05/3). MI in the bilateral cerebellar hemisphere were also decreased in patients compared with controls. After the treatment, the lower NAA, Glx and MI in ACC were normalized in MDD patients and the NAA and Glx increased compared to baseline values. The MI levels in the bilateral cerebellar hemisphere were also normalized in patients. MI and choline levels in the right cerebellar hemisphere were elevated compared to those at baseline. Our study suggests that metabolic abnormalities in the ACC and cerebellar hemisphere are implicated in MDD. Antidepressants may alter the local metabolic abnormalities in these areas.

1H magnetic resonance spectroscopy in the diagnosis of paediatric low grade brain tumours

IntroductionLow grade gliomas are the commonest brain tumours in children but present in a myriad of ways, each with its own treatment challenges. Conventional MRI scans play an important role in their management but have limited ability to identify likely clinical behaviour. The aim of this study is to investigate 1H magnetic resonance spectroscopy (MRS) as a method for detecting differences between the various low grade gliomas and related tumours in children. Patients and methodsShort echo time single voxel 1H MRS at 1.5 or 3.0T was performed prior to treatment on children with low grade brain tumours at two centres and five MR scanners, 69 cases had data which passed quality control. MRS data was processed using LCModel to give mean spectra and metabolite concentrations which were compared using T-tests, ANOVA, Receiver Operator Characteristic curves and logistic regression in SPSS. ResultsSignificant differences were found in concentrations of key metabolites between glioneuronal and glial tumours (T-test p<0.05) and between most of the individual histological subtypes of low grade gliomas. The discriminatory metabolites identified, such as choline and myoinositol, are known tumour biomarkers. In the set of pilocytic astrocytomas and unbiopsied optic pathway gliomas, significant differences (p<0.05, ANOVA) were found in metabolite profiles of tumours depending on location and patient neurofibromatosis type 1 status. Logistic regression analyses yielded equations which could be used to assess the probability of a tumour being of a specific type. ConclusionsMRS can detect subtle differences between low grade brain tumours in children and should form part of the clinical assessment of these tumours.

Brain dynamic neurochemical changes in dystonic patients: A magnetic resonance spectroscopy study

Measurements of the concentrations of γ-aminobutyric acid (GABA) and glutamate in the motor cortices and lentiform nuclei of dystonic patients using single-voxel (1)H magnetic resonance spectroscopy (MRS) have yielded conflicting results so far. This study aimed to investigate dynamic changes in metabolite concentrations after stimulation of the motor cortices in patients with upper limb dystonia. Using single-voxel MRS at 3 T, the concentrations of GABA, glutamate plus glutamine, and N-acetylaspartate were measured bilaterally in the primary sensorimotor cortex, lentiform nucleus, and occipital region before and after 5-Hz transcranial magnetic stimulation (TMS) over the dominant motor cortex. Data obtained from 15 patients with upper limb primary dystonia were compared with data obtained from 14 healthy volunteers. At baseline, there was no group difference in concentration of metabolites in any region. rTMS induced a local (in the stimulated motor cortex) decrease of N-acetylaspartate (P < .006) to the same extent in healthy volunteers and patients. GABA concentrations were modulated differently, however, decreasing mildly in patients and increasing mildly in healthy volunteers (P = .05). There were no remote effects in the lentiform nucleus in either group. The stimulation-induced changes in metabolite concentrations have been interpreted in view of the increased energy demand induced by rTMS. The dynamics of the GABA concentration were specifically impaired in dystonic patients. Whether these changes reflect changes in the extrasynaptic or synaptic GABA component is discussed.

Predictive and Diagnostic Capabilities of Noninvasive MR Technology in Non-Hodgkin Lymphoma Patients.

Abstract 2701Because of the wealth of information obtained using MR technology, this technique promises to be one of the best imaging methods in cancer. In addition, MR technology is fairly noninvasive and does not require ionizing radiation or radioactivity, making it one of the safest imaging modalities available. This study aims to evaluate the predictive and diagnostic capabilities of a multimodality MR exam to study non-Hodgkin lymphoma (NHL) patients. Experimental Design:Under ethical review board approval, a pretreatment MR exam was obtained in NHL patients, which included clinical MRI, diffusion weighted imaging (DWI), 1H MR spectroscopy (MRS) and/or 31P MRS. Using 3D-localized, 1H-irradiated 31P MRS the phosphomonoester (PME) levels normalized to nucleoside triphosphates (PME/NTP) were measured. Using single voxel 1H MRS the tumor total choline to water (tCho/H2O) ratio was determined. DWI was acquired using echo-planar imaging with fat suppression and b-values of 0 and 1000 s/mm2 to obtain the apparent diffusion constant (ADC) of water in the tumor. In regard to clinical information, treatment response was assessed six-months after treatment and the patients grouped as those with a complete response (CR) and those without a complete response (NCR). Time to treatment failure (TTF), was measured as the time between the end of one treatment and the start of a new one. Results:Pretreatment PME/NTP values were measured in 59 newly diagnosed NHL patients. Twenty-seven of these patients were diffuse large B-cell lymphoma (DLBCL) patients. From these patients, 20 were treated with CHOP or equivalent therapy. The significantly different mean pretreatment PME/NTP values (SD, n) for CR and NCR were 1.42 (0.41, 13) and 2.46 (0.40, 7), respectively (p<0.00001), with sensitivity and specificity of 0.85 in a Fisher test (p<0.01). PME/NTP correlated with TTF by Cox (p<0.02) and Kaplan-Meier tests (p<0.00001). The additional seven DLBCL patients were treated with added rituximab also showing significantly different mean pretreatment PME/NTP values: CR, 1.56 (0.61, 4) vs. NCR, 3.18 (0.41,3), (p<0.02), as well as Kaplan-Meier curves for TTF (p < 0.01). The remaining 32 patients with other forms of NHL were studied together. Again in this group of patients, the PME/NTP was significantly different in the response groups: CR, 1.41 (0.35, 5) vs. NCR, 2.11 (0.16, 27), p<0.04. In seven NHL patients the correlation of the PME/NTP values determined by 31P MRS vs. the tCho/H2O values determined by 1H MRS prior to receive treatment showed a statistically significant linear regression (y = 0.16× – 0.77, r2 = 0.7, p < 0.005). DWI was obtained in 15 NHL patients refractory to previous treatments demonstrating that the mean ADC value of refractory NHL patients is lower than the one in normal volunteers (0.91 [0.23, 15] vs. 1.13 [0.14, 10], p<0.01), but similar to those reported from newly diagnosed patients. Discussion:Our data validate the capabilities of a multimodality MR exam to study NHL patients by demonstrating that: 1) the pretreatment tumor PME/NTP levels predict both responses to treatment and TTF in different histological subtypes of NHL patients; 2) the correlation of PME/NTP with tCho/H2O that suggests that prediction of treatment outcome may also be possible using the ratio determined by 1H MRS, which will allow to use the increased sensitivity of 1H MRS; 3) the potential additional information provided by the simultaneous determination of 31P and 1H MRS; and 4) our preliminary DWI results suggesting that for newly diagnosed and refractory NHL patients, the quantitative ADC evaluation can aid assessing malignant masses and differentiate them from normal lymph nodes. Disclosures:No relevant conflicts of interest to declare.

Magnetic resonance spectroscopy metabolite profiles predict survival in paediatric brain tumours

BackgroundBrain tumours cause the highest mortality and morbidity rate of all childhood tumour groups and new methods are required to improve clinical management. 1H magnetic resonance spectroscopy (MRS) allows non-invasive concentration measurements of small molecules present in tumour tissue, providing clinically useful imaging biomarkers. The primary aim of this study was to investigate whether MRS detectable molecules can predict the survival of paediatric brain tumour patients. Patients and methodsShort echo time (30ms) single voxel 1H MRS was performed on children attending Birmingham Children’s Hospital with a suspected brain tumour and 115 patients were included in the survival analysis. Patients were followed-up for a median period of 35months and Cox-Regression was used to establish the prognostic value of individual MRS detectable molecules. A multivariate model of survival was also investigated to improve prognostic power. ResultsLipids and scyllo-inositol predicted poor survival whilst glutamine and N-acetyl aspartate predicted improved survival (p<0.05). A multivariate model of survival based on three MRS biomarkers predicted survival with a similar accuracy to histologic grading (p<5e–5). A negative correlation between lipids and glutamine was found, suggesting a functional link between these molecules. ConclusionsMRS detectable biomolecules have been identified that predict survival of paediatric brain tumour patients across a range of tumour types. The evaluation of these biomarkers in large prospective studies of specific tumour types should be undertaken. The correlation between lipids and glutamine provides new insight into paediatric brain tumour metabolism that may present novel targets for therapy.

Non-invasive diagnosis of lung tuberculosis in children by single voxel 1H-magnetic resonance spectroscopy

Our previous study showed that (1)H-magnetic resonance spectroscopy ((1)H-MRS) can detect lipid peaks characteristic for Mycobacterium tuberculosis infection in cerebral lesions of young children; therefore, we aimed to extend and validate the application of (1)H-MRS for the diagnosis of active pulmonary tuberculosis lesions in three adolescent patients. Here, we document lipid peaks characteristic for M. tuberculosis infection by (1)H-MRS from lung tissue surrounding lung cavities of two patients whose sputum samples were positive for acid-fast bacilli by microscopy and positive for M. tuberculosis by genetic testing, indicating active tuberculosis. A similar lipid peak was found also in the pleural effusion of a third patient with concurrent lung cavity compatible with active tuberculosis. However, in a patient with a pyogenic pulmonary abscess, (1)H-MRS of the drained pus displayed different characteristic peaks but no lipid peak at all. Our findings further validate (1)H-MRS as a rapid, non-invasive, and specific diagnostic tool for active tuberculosis in children with microbiologically documented infection outside the central nervous system, specifically in the lungs.

Metabolic dysfunction and relationship in human frontoparietal cortex in severe traumatic brain injury: Single-voxel 1H magnetic resonance spectroscopy study

(1)H-magnetic resonance spectroscopy revealed that apparently normal (from the data of magnetic resonance imaging) human brain frontoparietal cortex in the subacute stage of traumatic brain injury is characterized by decreased level of N-acetylaspartate (NAA) and increase in levels of myoinositol, choline-containing compounds (Cho), and creatine/phosphocreatine (Cr). Correlations between Cr, Cho, and NAA were established. We propose a scheme of neuronal metabolic processes that joins these substances.