MR spectroscopy

ingle-voxel proton MR spectroscopy ( 1 H-MRS) of the breast is occasionally used to investigate the chemical composition of breast tumors [1]. It was reported that a choline peak at 3.25 ppm may be used as an indicator of malignancy, and the presence or absence of the choline peak increases the specificity of differentiating benign from malignant breast lesions, thus reducing unnecessary biopsies [1]. MRI is sometimes used as a screening tool for evaluation of breast tissue changes using various techniques for presumably normal breasts in asymptomatic women . Reichenbach et al. [9] reported that 3D MRI using a segmentation algorithm and a histogram was able to detect and quantify breast tissue changes before and during hormonal replacement therapy. Single-voxel proton MR spectroscopy has been applied to ex vivo normal breast tissue to

Background Drug resistance has been a global burden in the management of epilepsy. It is desirable if this could be predicted earlier in the course of management to give time for alternative and a more definitive mode of management, such as epilepsy surgeries. Methods We conducted a systematic review and meta-analysis to investigate the relationship between elevated age at the onset of the first seizure or cortical imaging abnormalities and the development of drug resistance in epilepsy. We performed a systematic search in PubMed, EMBASE, and SCOPUS databases for studies investigating the predictive utility of age of onset or cortical imaging abnormalities on drug resistance. Results Odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted and analyzed by the RevMan 5.4 software. Meta-analysis was done across 12 studies involving 5315 patients. Age of onset of seizures younger than 5 years was found to be associated with the development of drug resistance (OR: 0.685, 95% CI 0.410-0.960), also cortical imaging abnormalities were found to be associated with the development of drug resistance. Conclusion Children with early onset seizures could better from neurosurgical management than pharmacological management as the early age of onset was associated with drug resistance and cortical abnormalities on neuroimaging could be an indication for neurosurgical management of epilepsies.

Both severe impairments of brain development in untreated infants and acute reversible neurotoxic effects on brain function are clinical features of phenylketonuria (PKU). For determining whether impairments of cerebral energy metabolism play a role in the pathophysiology of PKU, quantitative in vivo 31 P magnetic resonance spectroscopy (MRS) was performed in a supratentorial voxel of 11 adult PKU patients and controls. Peak areas of inorganic phosphate; phosphocreatine; ␣-, ␤-, and ␥-ATP; NAD; phosphomonoesters; phosphodiesters; and a broad phospholipid signal were converted to millimolar concentrations. Mg 2ϩ , pH, ADP, the phosphorylation potential, and the relative velocity of oxidative metabolism V/V max were derived. Clinical evaluation included mutation analysis, neurologic investigation, intelligence testing, magnetic resonance imaging, and concurrent plasma and brain phenylalanine (Phe), the last by 1 H-MRS. Phe loading was performed in five patients with an oral dose of 100 mg/kg body wt L-Phe monitored by spectral EEG analysis. Under steadystate conditions, 31 P-MRS revealed normal values for ATP, phosphocreatine, NAD, phosphomonoesters, phosphodiesters, Mg 2ϩ , and pH in PKU. ADP (ϩ11%) and the phosphorylation potential (ϩ22%) were increased. Peak areas of inorganic phosphate (Ϫ22%) and phospholipid (Ϫ8%) were decreased. ADP correlated with concurrent plasma (r ϭ 0.65) and brain (r ϭ 0.55) Phe. During the Phe load, blood Phe levels increased steeply. EEG revealed slowing of background activity. The phosphorylation potential decreased, whereas ADP and V/V max increased. In vivo 31 P-MRS demonstrated subtle abnormalities of cerebral energy metabolism in PKU in steady-state conditions that were accentuated by a Phe load, indicating a link between Phe neurotoxicity and imbalances of cerebral energy metabolism. (Pediatr Res 53: 654-662, 2003) Abbreviations 1 H-MRS, proton magnetic resonance spectroscopy IDC, index of dietary control MPF, mean power frequency MRI, magnetic resonance imaging P I , inorganic phosphate PAH, phenylalanine hydroxylase PCr, phosphocreatine PDE, phosphodiesters Phe, phenylalanine PL, phospholipids PME, phosphomonoesters 31 P-MRS, phosphorus-31 magnetic resonance spectroscopy PKU, phenylketonuria PP, phosphorylation potential Phenylketonuria (PKU) is the most frequent inborn disorder of amino acid metabolism. PKU is caused by an autosomal recessively transmitted deficiency of hepatic phenylalanine (Phe) hydroxylase (PAH; enzyme commission 1.14.16.1). In untreated PKU patients, Phe accumulates to plasma levels exceeding 1500 M; normal plasma Phe in fasting adults is ~60 M. The characteristics of untreated PKU result from disturbed brain development and include microcephaly, epilepsy, severe mental retardation, and behavior problems (1). Through the early start of a Phe-restricted diet, the phenotype of untreated PKU can be widely prevented. However, elevated plasma concentrations of Phe, which usually occur in adolescence because of a relaxed diet, are known to cause acute impairments of brain function. Reduced attentional abilities, slow information processing, and typical changes in the

As a model for guanidinoacetate methyltransferase (GAMT) deficiency in humans, a gene knockout mouse model was generated. Here we report on several metabolic abnormalities in these mice, observed by in vivo and in vitro MR spectroscopy. In 1H MR spectra of brain and hindleg muscle a clearly reduced signal of creatine (Cr) was observed in GAMT‐deficient (GAMT–/–) animals. Analysis of the 1H MR spectra of GAMT–/– brain indicated little or no increase of a signal for guanidinoacetate (Gua). In proton MR spectra of muscle, a broad signal of low intensity was observed for Gua. However, substantial Gua accumulation in intact muscle tissue was unequivocally confirmed in high‐resolution magic angle spinning spectra, in which the Gua signal was resolved as one clear sharp singlet. In 31P MR analysis of brain and hindleg muscle a strongly reduced phosphocreatine (PCr) content was shown. In addition, a signal of phosphorylated Gua at 0.5 ppm upfield of PCr was observed, with much higher intens...

Segmentation of the prostate boundary on clinical images is useful in a large number of applications including calculating prostate volume during biopsy, tumor estimation, and treatment planning. Manual segmentation of the prostate boundary is, however, time consuming and subject to inter-and intra-reader variability. Magnetic Resonance (MR) imaging (MRI) and MR Spectroscopy (MRS) have recently emerged as promising modalities for detection of prostate cancer in vivo. In this paper we present a novel scheme for accurate and automated prostate segmentation on in vivo 1.5 Tesla multi-modal MRI studies. The segmentation algorithm comprises two steps: (1) A hierarchical unsupervised spectral clustering scheme using MRS data to isolate the region of interest (ROI) corresponding to the prostate, and (2) an Active Shape Model (ASM) segmentation scheme where the ASM is initialized within the ROI obtained in the previous step. The hierarchical MRS clustering scheme in step 1 identifies spectra corresponding to locations within the prostate in an iterative fashion by discriminating between potential prostate and non-prostate spectra in a lower dimensional embedding space. The spatial locations of the prostate spectra so identified are used as the initial ROI for the ASM. The ASM is trained by identifying user-selected landmarks on the prostate boundary on T2 MRI images. Boundary points on the prostate are identified using mutual information (MI) as opposed to the traditional Mahalanobis distance, and the trained ASM is deformed to fit the boundary points so identified. Cross validation on 150 prostate MRI slices yields an average segmentation sensitivity, specificity, overlap, and positive predictive value of 89%, 86%, 83%, and 93% respectively. We demonstrate that the accurate initialization of the ASM via the spectral clustering scheme is necessary for automated boundary extraction. Our method is fully automated, robust to system parameters, and computationally efficient.

Segmentation of the prostate boundary on clinical images is useful in a large number of applications including calculation of prostate volume pre-and post-treatment, to detect extracapsular spread, and for creating patient-specific anatomical models. Manual segmentation of the prostate boundary is, however, time consuming and subject to inter-and intra-reader variability. T2-weighted (T2-w) magnetic resonance (MR) structural imaging (MRI) and MR spectroscopy (MRS) have recently emerged as promising modalities for detection of prostate cancer in vivo. MRS data consists of spectral signals measuring relative metabolic concentrations, and the metavoxels near the prostate have distinct spectral signals from metavoxels outside the prostate. Active Shape Models (ASM's) have become very popular segmentation methods for biomedical imagery. However, ASMs require careful initialization and are extremely sensitive to model initialization. The primary contribution of this paper is a scheme to automatically initialize an ASM for prostate segmentation on endorectal in vivo multi-protocol MRI via automated identification of MR spectra that lie within the prostate. A replicated clustering scheme is employed to distinguish prostatic from extra-prostatic MR spectra in the midgland. The spatial locations of the prostate spectra so identified are used as the initial ROI for a 2D ASM. The midgland initializations are used to define a ROI that is then scaled in 3D to cover the base and apex of the prostate. A multi-feature ASM employing statistical texture features is then used to drive the edge detection instead of just image intensity information alone. Quantitative comparison with another recent ASM initialization method by Cosio showed that our scheme resulted in a superior average segmentation performance on a total of 388 2D MRI sections obtained from 32 3D endorectal in vivo patient studies. Initialization of a 2D ASM via our MRS-based clustering scheme resulted in an average overlap accuracy (true positive ratio) of 0.60, while the scheme of Cosio yielded a corresponding average accuracy of 0.56 over 388 2D MR image sections. During an ASM segmentation, using no initialization resulted in an overlap of 0.53, using the Cosio based methodology resulted in an overlap of 0.60, and using the MRS-based methodology resulted in an overlap of 0.67, with a paired Student's t-test indicating statistical significance to a high degree for all results. We also show that the final ASM segmentation result is highly correlated (as high as 0.90) to the initialization scheme.

Background and Purpose-Previous 31 P-magnetic resonance spectroscopy ( 31 P-MRS) studies have shown that cerebral cortical energy metabolism is abnormal in migraine and that cortical energy reserves decrease with increasing severity and duration of aura. Migrainous infarction is a rare complication of migraine with aura, and its pathophysiology is poorly understood. We used 31 P-MRS to determine whether migrainous stroke shows similar interictal abnormalities in cortical energy metabolism as severe, prolonged aura. Methods-We used 31 P-MRS to study patients with a diagnosis of either migrainous infarction or migraine with persistent aura without infarction (aura duration Ͼ7 days) according to International Headache Society criteria. We compared clinical presentation and metabolite ratios between patient groups. We also studied healthy controls with no history of migraine. Results-Patients with persistent aura without infarction had lower phosphocreatine-phosphate (PCr/Pi) ratios (meanϮSD, 1.61Ϯ0.10) compared with controls (1.94Ϯ0.35, Pϭ0.011) and with patients with migrainous stroke (1.96Ϯ0.16, PϽ0.0001). These differences were present in cortical tissue only. In migrainous stroke patients, the metabolite ratios did not differ significantly from those of controls without migraine. Conclusions-The differences in cortical energy reserves between patients with migrainous stroke and in those with migraine with persistent aura suggest that the pathomechanisms of these conditions differ and that migrainous infarction does not simply represent a particularly severe form of migrainous aura. This finding supports the revised International Headache Society criteria, which now distinguish between migrainous infarction and migraine with persistent aura without infarction. (Stroke. 2009;40:3740-3744.

Cardiomyopathy is a frequent cause of morbidity and mortality in patients carrying the A3243G transition in the mitochondrial DNA (mtDNA) tRNALeu(UUR) gene, the most common heteroplasmic single mtDNA defect. We used phosphorus magnetic resonance spectroscopy ( 31 P-MRS) to look for evidence of an in vivo bioenergetics defect in patients carrying the A3243G mtDNA mutation with and without echocardiographic signs of left ventricle hypertrophy (LVH). Eight patients, three with LVH, carrying the A3243G mtDNA mutation and 10 healthy subjects underwent one-dimensional chemical shift imaging 31 P-MRS. In the patients, mean cardiac phosphocreatine to adenosine triphosphate ratio (PCr/ATP) (1.55 F 0.58) was significantly reduced compared to the control group (2.34 F 0.14; P < 0.001). Cardiac PCr/ATP was within the normal range only in one case that showed normal echocardiography. Our results point to a central role of bioenergetics deficit in the development of cardiac hypertrophy in patients with the A3243G mtDNA mutation. Impaired cardiac energy metabolism in patients with normal echocardiography suggests that the enhancement of mitochondrial function may be beneficial not only to patients with cardiac hypertrophy but also to those patients carrying the mutation in the absence of signs of cardiac hypertrophy and/or dysfunction but with cardiac bioenergetics deficit.

To determine whether the proton spectra from patients with clinically diagnosed Parkinson disease differ from the spectra of age-matched healthy subjects with respect to the major cerebral metabolite resonances as well as lactate. Fourteen patients with Parkinson disease (38 to 81 years of age) and 13 healthy control subjects (37 to 81 years of age) were studied using image-guided, single-voxel (27-cm3 volume) proton MR spectroscopy of the occipital lobe. The peak area ratios of N-acetyl aspartate to creatine and N-acetyl aspartate to choline for Parkinson patients did not show a statistically significant difference from the corresponding ratios for control subjects. There was a very significant increase in the ratio of lactate to N-acetyl aspartate for patients with Parkinson disease, with the greatest increase (threefold) manifested by the subgroup (n = 4) with dementia. The difference in N-acetyl aspartate to choline between women (n = 7) with Parkinson disease and healthy women ...

BackgroundDeficiency of 4‐aminobutyrate aminotransferase (GABA‐T) is a rare disorder of GABA catabolism, with only a single sibship reported. We report on a third case, a Japanese female infant with severe psychomotor retardation and recurrent episodic lethargy with intractable seizures, with the diagnosis facilitated by proton magnetic resonance (MR) spectroscopy (1H‐MRS).MethodsNeuroimaging was performed at the first episode of lethargy. For 1H‐MRS, locations were placed in the semioval center and the basal ganglia. Quantification of metabolite concentrations were derived using the LCModel. We confirmed the diagnosis subsequently by enzyme and molecular studies, which involved direct DNA sequence analysis and the development of a novel multiplex ligation‐dependent probe amplification test.Results1H‐MRS analysis revealed an elevated GABA concentration in the basal ganglia (2.9 mmol/l). Based on the results of quantitative 1H‐MRS and clinical findings, GABA‐T deficiency was suspecte...

Post-operative quadriplegia is a rarely encountered complication and not previously reported as the initial presentation of tumefactive multiple sclerosis. We present an unusual case of a patient with such manifestation and atypical lesions on brain magnetic resonance imaging. The patient was treated with methyl prednisolone pulse therapy and showed a dramatic response. Uncommon neurologic diseases can have very unusual presentations, which should be taken into consideration when encountered with such patients. Considering this fact will help physicians in better decision-making and proper treatment planning.

This study aimed to evaluate metabolite ratios in the brain parenchyma of patients with subacute sclerosing panencephalitis (SSPE) using magnetic resonance spectroscopy (MRS). The study compared 32 children diagnosed with SSPE with a control group of 20 healthy children. Comparisons were made between the study and control groups and between children who had various stages of the disease, as well as between MRS values obtained from the frontal subcortical white matter and parieto-occipital white matter regions by multivoxel MRS imaging. MRS may make a contribution to diagnosis and follow-up of children with SSPE as findings reflecting neuronal loss may be revealed by this imaging technique.

Magnetic resonance imaging (MRI) evaluation of the developing brain has dramatically increased over the last decade. Faster acquisitions and the development of advanced MRI sequences, such as magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), perfusion imaging, functional MR imaging (fMRI), and susceptibility-weighted imaging (SWI), as well as the use of higher magnetic field strengths has made MRI an invaluable tool for detailed evaluation of the developing brain. This article will provide an overview of the use and challenges associated with 1.5-T and 3-T static magnetic fields for evaluation of the developing brain. This review will also summarize the advantages, clinical challenges, and safety concerns specifically related to MRI in the fetus and newborn, including the implications of increased magnetic field strength, logistics related to transporting and monitoring of neonates during scanning, and sedation considerations, and a discussion of current technol...

BACKGROUND AND PURPOSE: Ketone bodies provide important alternate fuel for brain metabolism, and their transport into the brain increases with prolonged fasting. During diabetic ketoacidosis (DKA), serum ketone concentrations markedly increase; however, little is known about whether ketone bodies accumulate in cerebral tissues during DKA. We used proton MR spectroscopy (MRS) to detect cerebral -hydroxy butyrate (OHB) and acetone/ acetocaetate (AcAc) in children with DKA. METHODS: Twenty-five children underwent brain MRS: nine within 4 hours of the start of treatment for DKA; 11, at 4-8 hours; and five, at 8-12 hours. MRS was repeated after their recovery from the DKA episode at &gt;72 hours after the start of treatment. MRS was evaluated for peaks corresponding to OHB (doublet centered on 1.20 ppm) and lactate (doublet centered on 1.33 ppm). Difference spectroscopy was used to identify the AcAc peak at 2.22-2.26 ppm. RESULTS: OHB was detected in 13 children (52%), more frequently wi...

BACKGROUND AND PURPOSE: Subclinical cerebral edema occurs in many, if not most, children with diabetic ketoacidosis (DKA) and may be an indicator of subtle brain injury. Brain ratios of N-acetylas- partate (NAA) to creatine (Cr), measured by proton MR spectroscopy, decrease with neuronal injury or dysfunction. We hypothesized that brain NAA/Cr ratios may be decreased in children in DKA, indicating subtle neuronal injury. MATERIALS AND METHODS: Twenty-nine children with DKA underwent cerebral proton MR spectros- copy during DKA treatment (2-12 hours after initiating therapy) and after recovery from the episode (72 hours or more after the initiation of therapy). We measured peak heights of NAA, Cr, and choline (Cho) in 3 locations within the brain: the occipital gray matter, the basal ganglia, and periaqueductal gray matter. These regions were identified in previous studies as areas at greater risk for neurologic injury in DKA-related cerebral edema. We calculated the ratios of NAA/Cr...

We assessed the ability of 11 C-acetate PET/CT, MRI, and proton MR spectroscopy ( 1 H-MRS) to image localized prostate cancer and detect its aggressiveness, using qualitative and quantitative approaches. Methods: Twenty-one patients with untreated localized prostate cancer, diagnosed using transrectal ultrasound-guided biopsy, were prospectively enrolled. Cancer laterality was based on the percentage of cancer and the highest Gleason score determined from biopsies. In addition to PET/CT, 3-dimensional 1 H-MRS of the entire prostate volume using a quantitative approach was performed. The imaging and histologic findings of 8 patients undergoing subsequent prostatectomy were compared on a sextant level. For each lobe and sextant, standardized uptake values (SUVs) and (choline 1 creatine 1 polyamines)-to-citrate (CCP/C) ratios were obtained from 11 C-acetate PET/CT and 1 H-MRS, respectively. The visual and quantitative findings on PET/CT and MRI data were compared with cancer laterality and aggressiveness based on the Gleason score and with prostate-specific antigen (PSA) velocity and international risk group classification. Results: The sensitivity, specificity, and accuracy, on a lobar level using visual analysis, of 11 C-acetate PET/CT were 80%, 29%, 71%, respectively, and 89%, 29%, 79%, respectively, using contrastenhanced MRI. The sensitivity and accuracy of 11 C-acetate PET/CT decreased to 64% and 63% and specificity increased to 62% when sextant analysis was performed. The agreement between prostate cancer laterality based on biopsy findings and visual interpretation of 11 C-acetate PET/CT and contrastenhanced MRI was similar at 71%. The mean SUV maximum and CCP/C maximum for the dominant tumor lesion were 5.5 and 1.48, respectively, and did not differ significantly from values in the nondominant lobe. The dominant-lesion SUVs or CCP/C values were not associated with histologically determined prostate cancer aggressiveness, nor did PSA velocity correlate with the SUV or CCP/C values from the entire gland. 11 C-acetate PET/CT, MRI, and 1 H-MRS enable detection of localized prostate cancer with comparable and limited accuracy but fail to provide information on cancer aggressiveness.

Meningiomas limited to the internal auditory canal (IAC) are rare. Acoustic neuroma is usually the diagnosis made when a tumor is found in this location because of its higher frequency. We report on a 58 year-old woman with a meningioma arising from the IAC and the difficulty to establish the pre-surgical diagnosis, based on clinical and radiological features. The perioperative suspicion and confirmation are very important to deal with the dura and bone infiltration in order to reduce tumor recurrence.

Concomitant tubercular and fungal cerebellar abscess is rare and we report the first concomitant recurrent multi-lobulated tubercular and fungal cerebellar abscess in an immunocompromised girl with Histiocytosis-X. She presented with cerebellar abscess history diagnosed during the ongoing treatment for tuberculous meningitis. The abscess was drained. Upon the detection of cerebellar abscess recurrence and pulmonary infection, she was referred to our clinic five weeks after the first surgical intervention. Patient was conscious, co-operating but confused. She had severe cachexia, stiff neck and fever. Fundus examination showed bilateral papilledema. Cranial MR images revealed multiple lobulated lesions. Suboccipital craniectomy was performed and abscess was evacuated in toto. Lesion was multi-lobulated. Thick, yellow-gray purulent material was drained. Histopathological examinations yielded Langhans giant cells,budding and branching fungal structures. Fungal infection was identified. We emphasize that posterior decompression and total resection should be considered first in the management of lesions with mass effect in the posterior fossa. Also the presence of concomitant fatal fungal abscess highlights that although the clinic and former diagnoses of the patient may direct the clinician to a certain pathogen, unusual resistant organisms should not be.

Background: Glycogen storage disease (GSD) type IX, due to the deficiency of hepatic phosphorylase b kinase, results in liver enlargement, growth retardation and fasting ketosis. Though, many patients with this disorder are asymptomatic and do not require treatment, a number of patient can develop liver cirrhosis and growth retardation. Early diagnosis and treatment with cornstarch may prevent liver cirrhosis and promote better growth and development. This is a case report of the first documented GSD IXa in a Filipino boy who was evaluated for suboptimal growth. Methods: MT is the 2nd child of healthy and nonconsanguineous parents. He was noted to have a prominent abdomen since birth, but without organomegaly. He had been reported slightly shorter than his peers, hence was brought to medical attention at 9 years of age. Results: Diagnostic evaluation revealed no Kayser-Fleischer ring, but hepatomegaly with mildly elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and ammonia levels. Liver biopsy revealed microvesicular steatosis. Whole exome sequencing with specific analysis of the phosphorylase kinase alpha-2 subunit (PHKA2) gene documented hemizygous state of a previously reported variant, c.3614 C>T (p.P1205L). Diet therapy with cornstarch was started and the patient is on regular follow up. Conclusions: DNA analysis prompted by clinical and pathologic findings led to the definitive diagnosis of GSD type IX.

Objectives: This study compares proton magnetic resonancespectroscopic imaging (1H-MRSI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) combined techniques at 3 T magnet versus [( )F]choline PET/computed tomography (CT) in the detection of local prostate cancer recurrence in patients with biochemical progression after radical retropubic prostatectomy (RRP). Materials and methods: 84 consecutive patients at high risk of local recurrence underwent combined 1HMRSI-DCEMR and 18-Fcholine-PET/CT. MR scan protocol included turbo spin echo (TSE) T2-weighted sequences in the axial, sagittal and coronal planes; three-dimensional (3D) chemical shift imaging (CSI) sequences with spectral/spatial pulses optimized for quantitative detection of choline and citrate; dynamic contrast enhanced gradient-echo (GRE) T1-weighted sequence. The population was divided into two groups. Group A included 28 patients with a lesion size ranging between 5.00 mm and 7.2 mm and PSA reduction following radiation therapy. Group B included 56 patients with a lesion size between 7.6 mm and 19.4 mm. Sensitivity, specificity, positive predictive value (PPV) and accuracy were evaluated and receiver operating characteristic (ROC) curves were performed. Results: In Group A combined 1H-MRSI and DCE-MRI showed a sensitivity of 92%, a specificity of 75% (PPV 96%) while PET-CT examination showed a sensitivity of 62% and a specificity of 50% (PPV 88%) in identifying local recurrence. The accuracy of MRI was 89% while PET-CT showed an accuracy of 60%. Areas under the ROC curve (AUC) values for MR and PET-CT were 0.833 and 0.562, respectively. In Group B combined 1H-MRSI and DCEMR showed a sensitivity of 94% and a specificity of 100% (PPV 100%) with accuracy of 94%. PET-CT had a sensitivity of 92% and a specificity of 33% (PPV 98%) with accuracy of 91%. The AUCs for MR and PET-CT values were 0.971 and 0.837, respectively. Conclusion: The diagnostic accuracy of combined 1HMRSI-DCEMR was higher than PET/CT to identify local prostate cancer recurrence, mostly in patients with low biochemical progression after RRP (0.2-2 ng/mL).

MR spectroscopy results in a mild case of guanidinoacetate methyltransferase (GAMT) deficiency are presented. The approach differs from previous MRS studies in the acquisition of a chemical shift imaging spectral map showing gray and white matter with the corresponding spectra in one overview. MR spectroscopy revealed guanidinoacetate (GAA) in the absence of creatine. New is that GAA signals are more prominent in gray matter than in white. In the prevailing view, that enzyme deficiency is localized in liver and pancreas and that all GAA is transported into the brain from the blood and the cerebrospinal fluid, this would be compatible with a more limited uptake and/or better clearance of GAA from the white matter compared to the grey matter.

In neuro-oncology, a major problem is clear identification of tumor from the surrounding normal tissue. We hypothesized that we could use the blood oxygen level-dependent functional MR imaging (BOLD fMRI) signals from tumors and normal brain to identify the tumors and distinguish them from the surrounding brain. Fourteen patients with meningiomas, gliomas, and metastatic tumors were scanned before surgery. All subjects performed a motor task; 2 subjects were also scanned while in a resting state. The BOLD signals were taken from selected points within the tumor and from the surrounding normal brain and were analyzed by using correlation analysis to determine how closely they were related. The BOLD signals from all of the tumors were significantly different from those in the surrounding normal tissue. In meningiomas and gliomas, selection of a voxel in the tumor for signal-intensity analysis highlighted the entire tumor mass while excluding the normal tissue. The BOLD signal intensity was the same whether the subjects were motionless or finger tapping. CONCLUSIONS: Analysis of the BOLD signal intensity provides a relatively simple and straightforward method for identifying brain tumors and distinguishing them from normal tissue. This approach may be of use in neurosurgery.

Our aims were to evaluate the metabolic profiles of pediatric brain tumors with short echo time (TE) MR spectroscopy and absolute quantitation of metabolite concentrations (in mmol/kg of tissue) and to describe metabolic features that distinguish individual tumor types and that may help to improve preoperative diagnosis of specific tumors. MR imaging examinations of 60 patients with untreated brain tumors (14 medulloblastomas, 5 anaplastic astrocytomas, 3 low-grade astrocytomas, 17 pilocytic astrocytomas, 4 anaplastic ependymomas, 5 ependymomas, 3 choroid plexus papillomas, 3 choroid plexus carcinomas, and 6 pineal germinomas) were reviewed. Single-voxel proton MR spectroscopy with a TE of 35 ms was performed and absolute metabolite concentrations were determined by using fully automated quantitation. Taurine (Tau) was significantly elevated in medulloblastomas (P &lt; .00001) compared with all other tumors pooled (All Other). Tau was also observed consistently, at lower concentrati...

In a subset of in vivo MR spectra acquired from pediatric brain tumors, we have observed an unassigned peak. The goal of this study was to determine the molecule of origin, and the prevalence and concentration of this chemical in various pediatric brain tumors. Single-voxel point-resolved spectroscopy (PRESS) spectra from 85 patients with brain tumors and 469 control subjects were analyzed. Citrate seemed to be a likely candidate, and model spectra of citrate were added to the basis set of metabolites for automated processing with use of LCModel software. Absolute "apparent" concentrations of citrate and the Cramer-Rao lower bounds (CRLB), indicators for the reliability of detection, were determined. RESULTS: "Apparent" citrate was detected in 26 of 85 patients with CRLB of less than 25%. Diffuse intrinsic brain stem glioma (DIBSG) had the highest mean concentration (4.0 Ϯ 1.1 mmol/kg in all subjects), and 8 of 12 patients had CRLB less than 25%. A significant reduction of citrate (P Ͻ .01) was observed in 6 DIBSGs that had follow-up MR spectroscopy studies after radiation therapy. "Apparent" citrate with CRLB less than 25% was detected in 5 of 22 medulloblastomas (mean citrate, 2.9 Ϯ 2.2 mmol/kg), in 5 of 14 ependymomas (2.6 Ϯ 1.8 mmol/kg), 5 of 14 astrocytomas (1.9 Ϯ 1.2 mmol/kg), and 3 of 23 pilocytic astrocytomas (1.4 Ϯ 1.1 mmol/kg). In control subjects older than 6 months, CRLB less than 25% was not observed, whereas CRLB less than 25% was observed in 39 of 194 subjects younger than 6 months,. CONCLUSION: MR signal consistent with citrate was observed in pediatric brain tumors and in the developing brain of infants younger than 6 months.

Brain has a capacity for reorganization that enables use-dependent adaptations to acquire skills. Previous studies demonstrated morphometric and functional use-dependent changes in the brains of musicians. The purpose of this study was to investigate the differences in metabolite concentrations in the planum temporale, an area strongly associated with the processing of music perception, between trained musicians and non-musicians. We hypothesized that the microscopic changes leading to use-dependent adaptations in brain might cause neurometabolite changes that could be detected with quantitative proton MR spectroscopy. We performed quantitative proton MR spectroscopy in the left planum temporale of 10 musicians (six men and four women; age range, 20-37 years) and in those of 10 age- and sex-matched control subjects who had no musical training. We calculated the major metabolite concentrations in the left planum temporale. The difference in N-acetylaspartate (NAA) concentrations betw...

In vivo 31 P Magnetic Resonance Spectroscopy (MRS) measures phosphorus-containing metabolites that play an essential role in many disease processes. An advantage over 1 H MRS is that total choline can be separated into phosphocholine and glycerophosphocholine which have opposite associations with tumour grade. We demonstrate 31 P MRS can provide robust metabolic information on an acceptable timescale to yield information of clinical importance. Methods: All MRI examinations were carried out on a 3T whole body scanner with all 31 P MRS scans conducted using a dual-tuned 1 H/ 31 P head coil. Once optimised on phantoms, the protocol was tested in six healthy volunteers (four male and two female, mean age: 25 ± 2.7). 31 P MRS was then implemented on three children with optic pathway gliomas. Results: 31 P MRS on volunteers showed that a number of metabolite ratios varied significantly (p < 0.05 ANOVA) across different structures of the brain, whereas PC/GPC did not. Standard imaging showed the optic pathway gliomas were enhancing on T1-weighted imaging after contrast injection and have high tCho on 1 H MRS, both of which are associated with high grade lesions. 31 P MRS showed the phosphocholine/glycerophosphocholine ratio to be low (<0.6) which suggests low grade tumours in keeping with their clinical behaviour and the histology of most biopsied optic pathway gliomas. Conclusion: 31 P MRS can be implemented in the brain as part of a clinical protocol to provide robust measurement of important metabolites, in particular providing a greater understanding of cases where tCho is raised on 1 H MRS.

Background and aim-Friedreich's ataxia (FRDA) and ataxia with oculomotor apraxia type 2 (AOA2) are the two most frequent forms of autosomal recessive cerebellar ataxias. However, brain metabolism in these disorders is poorly characterized and biomarkers of the disease progression are lacking. We aimed at assessing the neurochemical profile of the pons, the cerebellar hemisphere and the vermis in patients with FRDA and AOA2 to identify potential biomarkers of these diseases.

Oral squamous cell carcinoma (SCC) represents more than 90% of all head and neck cancers as reported by Hermans (Cancer Imaging, 5(Spec No A), S52-S57, 2005), which draws attention of investigative research for novel predictive metabolic biomarkers to understand the malignancy induced biochemical perturbations occurring at molecular level. In the present work, proton HR-MAS NMR spectroscopic studies have been performed on resected human oral SCC tumor tissues, its neighboring margins and bed tissues (n = 159), obtained from 36 patients (n = 27 training set; n = 9 unknown test set), for the identification of metabolic fingerprints. The proton NMR spectra were then subjected to chemometric unsupervised PCA and supervised OSC-filtered PCA and PLS-DA multivariate analysis. Application of PLS-DA on orthogonally signal corrected training data-set (n = 120 tissue specimens; 27 patients) allowed [95% correct classification of malignant tissues from benign samples with [98% specificity and sensitivity. The OSC-PLS-DA model thus constructed was used to predict the class membership of unknown tissue specimens (n = 39) obtained from nine patients. These tissue samples were correctly predicted in its respective histological categories with 97.4% diagnostic accuracy. The regression coefficients obtained from OSC-filtered PLS-DA model indicated that malignant tissues had higher levels of glutamate, choline, phosphocholine, lactate, acetate, taurine, glycine, leucine, lysine, isoleucine and alanine, and lower levels of creatine and PUFA, representing altered metabolic processes (lipidogenesis, protein synthesis, and volume regulation) during tumor progression. Thus proton HR-MAS MR spectroscopy could efficiently identify the metabolic perturbations of malignant tumor from non-malignant bed and margins tissue specimens, which may be helpful in understanding the extent of tumor penetration in neighboring tissues.

BackgroundOverweight and obesity are major worldwide health concerns characterized by an abnormal accumulation of fat in adipose tissue (AT) and liver.PurposeTo evaluate the volume and the fatty acid (FA) composition of the subcutaneous adipose tissue (SAT) and the visceral adipose tissue (VAT) and the fat content in the liver from 3D chemical‐shift‐encoded (CSE)‐MRI acquisition, before and after a 31‐day overfeeding protocol.Study TypeProspective and longitudinal study.SubjectsTwenty‐one nonobese healthy male volunteers.Field Strength/SequenceA 3D spoiled‐gradient multiple echo sequence and STEAM sequence were performed at 3T.AssessmentAT volume was automatically segmented on CSE‐MRI between L2 to L4 lumbar vertebrae and compared to the dual‐energy X‐ray absorptiometry (DEXA) measurement. CSE‐MRI and MR spectroscopy (MRS) data were analyzed to assess the proton density fat fraction (PDFF) in the liver and the FA composition in SAT and VAT. Gas chromatography‐mass spectrometry (GC‐M...

Despite the ubiquity of G(M2) gangliosides accumulation in patients with late-onset G(M2) gangliosidosis (G(M2)G), the only clinical MR imaging-apparent brain abnormality is profound cerebellar atrophy. The goal of this study was to detect the presence and assess the extent of neuroaxonal injury in the normal-appearing gray and white matter (NAGM and NAWM) of these patients. During a single imaging session, 9 patients with late-onset G(M2)G and 8 age-matched normal volunteers underwent the following protocol: (1) T1- and T2-weighted and fluid-attenuated inversion recovery MR images, as well as (2) multivoxel proton MR spectroscopy (1H-MR spectroscopy) to quantify the distribution of the n-acetylaspartate (NAA), creatine (Cr), and choline (Cho), were obtained. The patients&#39; NAA levels in the thalamus (6.5 +/- 1.9 mmol/L) and NAWM (5.8 +/- 2.1 mmol/L) were approximately 40% lower than the controls&#39; (P = .003 and P = .005), whereas the Cr and Cho reductions ( approximately 30% ...

This study sought to correlate quantitative presurgical proton magnetic resonance spectroscopic imaging (1H- MRSI) and diffusion imaging (DI) results with quantitative histopathological features of resected glioma tissue. The primary hypotheses were (1) glioma choline signal correlates with cell density, (2) glioma apparent diffusion coefficient (ADC) correlates inversely with cell density, (3) glioma choline signal correlates with cell proliferative index. Eighteen

Chronic alcohol abuse results in morphological, metabolic, and functional brain damage which may, to some extent, be reversible with early effects upon abstinence. Although morphometric, spectroscopic, and neuropsychological indicators of cerebral regeneration have been described previously, the overall amount and spatial preference of early brain recovery attained by abstinence and its associations with other indicators of regeneration are not well established. We investigated global and local brain volume changes in a longitudinal two-timepoint study with T 1 -weighted MRI at admission and after short-term (6-7 weeks) sobriety follow-up in 15 uncomplicated, recently detoxified alcoholics. Volumetric brain gain was related to metabolic and neuropsychological recovery. On admission and after short-term abstinence, structural image evaluation using normalization of atrophy (SIENA), its voxelwise statistical extension to multiple subjects, proton MR spectroscopy ( 1 H-MRS), and neuropsychological tests were applied. Upon short-term sobriety, 1 H-MRS levels of cerebellar choline and frontomesial N-acetylaspartate (NAA) were significantly augmented. Automatically detected global brain volume gain amounted to nearly two per cent on average and was spatially significant around the superior vermis, perimesencephalic, periventricular and frontal brain edges. It correlated positively with the percentages of cerebellar and frontomesial choline increase, as detected by 1 H-MRS. Moreover, frontomesial NAA gains were associated with improved performance on the d2-test of attention. In 10 ageand gender-matched healthy control subjects, no significant brain volume or metabolite changes were observed. Although cerebral osmotic regulations may occur initially upon sobriety, significant increases of cerebellar choline and frontomesial NAA levels detected at stable brain water integrals and creatine concentrations, serum electrolytes and red blood cell indices in our patient sample suggest that early brain recovery through abstinence does not simply reflect rehydration. Instead, even the adult human brain and particularly its white matter seems to possess genuine capabilities for regrowth. Our findings emphasize metabolic as well as regionally distinct morphological capacities for partial brain recovery from toxic insults of chronic alcoholism and substantiate early measurable benefits of therapeutic sobriety. Further understanding of the precise mechanisms of this recovery may become a valuable model of brain regeneration with relevance for other disorders.

Chronic alcohol abuse results in morphological, metabolic, and functional brain damage which may, to some extent, be reversible with early effects upon abstinence. Although morphometric, spectroscopic, and neuropsychological indicators of cerebral regeneration have been described previously, the overall amount and spatial preference of early brain recovery attained by abstinence and its associations with other indicators of regeneration are not well established. We investigated global and local brain volume changes in a longitudinal two-timepoint study with T 1 -weighted MRI at admission and after short-term (6-7 weeks) sobriety follow-up in 15 uncomplicated, recently detoxified alcoholics. Volumetric brain gain was related to metabolic and neuropsychological recovery. On admission and after short-term abstinence, structural image evaluation using normalization of atrophy (SIENA), its voxelwise statistical extension to multiple subjects, proton MR spectroscopy ( 1 H-MRS), and neuropsychological tests were applied. Upon short-term sobriety, 1 H-MRS levels of cerebellar choline and frontomesial N-acetylaspartate (NAA) were significantly augmented. Automatically detected global brain volume gain amounted to nearly two per cent on average and was spatially significant around the superior vermis, perimesencephalic, periventricular and frontal brain edges. It correlated positively with the percentages of cerebellar and frontomesial choline increase, as detected by 1 H-MRS. Moreover, frontomesial NAA gains were associated with improved performance on the d2-test of attention. In 10 ageand gender-matched healthy control subjects, no significant brain volume or metabolite changes were observed. Although cerebral osmotic regulations may occur initially upon sobriety, significant increases of cerebellar choline and frontomesial NAA levels detected at stable brain water integrals and creatine concentrations, serum electrolytes and red blood cell indices in our patient sample suggest that early brain recovery through abstinence does not simply reflect rehydration. Instead, even the adult human brain and particularly its white matter seems to possess genuine capabilities for regrowth. Our findings emphasize metabolic as well as regionally distinct morphological capacities for partial brain recovery from toxic insults of chronic alcoholism and substantiate early measurable benefits of therapeutic sobriety. Further understanding of the precise mechanisms of this recovery may become a valuable model of brain regeneration with relevance for other disorders.

Background Acute disseminated encephalomyelitis (ADEM) is a demyelinating disorder of the central nervous system (CNS). Differentiating ADEM from other inflammatory disorders, such as multiple sclerosis, is not always conclusive using conventional MRI. Objective To evaluate longitudinal magnetic resonance spectroscopy (MRS) changes that distinguish ADEM from other inflammatory disorders. Materials and methods MRI/MRS scans were performed in seven patients with ADEM during the acute and chronic phases of the disease. Results Partial recovery was detected between the acute and chronic phases in choline/creatine ratio. Major elevation of lipids and reduction in myo-inositol/creatine ratio was detected in all patients during the acute phase, followed by a reduction in lipids peak and elevation above normal in myo-inositol/creatine ratio during the chronic phase. Consistent and unique MRS changes in metabolite ratios between the acute and chronic presentations of the disease were found. To the best of our knowledge, these patterns have not been described in other inflammatory disorders and might assist in the early diagnosis of ADEM.

Soccer is played by more than 250 million people worldwide. Repeatedly heading the ball may place soccer players at high risk for repetitive subconcussive head impacts (RSHI). This study evaluates the long-term effects of RSHI on neurochemistry in athletes without a history of clinically diagnosed concussion, but with a high exposure to RSHI. Eleven former professional soccer players (mean age 52.0 -6.8 years) and a comparison cohort of 14 age-and gender-matched, former non-contact sport athletes (mean age 46.9 -7.9 years) underwent 3T magnetic resonance spectroscopy (MRS) and neurocognitive evaluation. In the soccer players a significant increase was observed in both choline (Cho), a membrane marker, and myo-inositol (ml), a marker of glial activation, compared with control athletes. Additionally, ml and glutathione (GSH) were significantly correlated with lifetime estimate of RSHI within the soccer group. There was no significant difference in neurocognitive tests between groups. Results of this study suggest an association between RSHI in soccer players and MRS markers of neuroinflammation, suggesting that even subconcussive head impacts affect the neurochemistry of the brain and may precede neurocognitive changes. Future studies will need to determine the role of neuroinflammation in RSHI and the effect on neurocognitive function.

Multimodality imaging (such as PET-CT) is rapidly becoming a valuable tool in the diagnosis of disease and in the development of new drugs. Functional images produced with PET, fused with anatomical images created by MRI, allow the correlation of form with function. Perhaps more exciting than the combination of anatomical MRI with PET, is the melding of PET with MR Spectroscopy (MRS). Thus, two aspects of physiology could be combined in novel ways to produce new insights into the physiology of normal and pathological processes. Our team is developing a system to acquire MRI images and MRS spectra, and PET images contemporaneously. The prototype MR-compatible PET system consists of two opposed detector heads (appropriate in size for small animal imaging), operating in coincidence mode with an active field-of-view of ~14cm in diameter. Each detector consists of an array of LSO detector elements coupled through a 2m long fiber optic light guide to a single position-sensitive photomultiplier tube. The use of light guides allows these magnetic field-sensitive elements of the PET imager to be positioned outside the strong magnetic field of our 3T MRI scanner. The PET scanner imager was integrated with a 12cm diameter, 12-leg custom, birdcage coil. Simultaneous MRS spectra and PET images were successfully acquired from a multi-modality phantom consisting of a sphere filled with seventeen brain relevant substances and a positron-emitting radionuclide. There were no significant changes in MRI or PET scanner performance when both were present in the MRI magnet bore. This successful initial test demonstrates the potential for using such a multi-modality to obtain complementary MRS and PET data.

Background Acute disseminated encephalomyelitis (ADEM) is a demyelinating disorder of the central nervous system (CNS). Differentiating ADEM from other inflammatory disorders, such as multiple sclerosis, is not always conclusive using conventional MRI. Objective To evaluate longitudinal magnetic resonance spectroscopy (MRS) changes that distinguish ADEM from other inflammatory disorders. Materials and methods MRI/MRS scans were performed in seven patients with ADEM during the acute and chronic phases of the disease. Results Partial recovery was detected between the acute and chronic phases in choline/creatine ratio. Major elevation of lipids and reduction in myo-inositol/creatine ratio was detected in all patients during the acute phase, followed by a reduction in lipids peak and elevation above normal in myo-inositol/creatine ratio during the chronic phase. Consistent and unique MRS changes in metabolite ratios between the acute and chronic presentations of the disease were found. To the best of our knowledge, these patterns have not been described in other inflammatory disorders and might assist in the early diagnosis of ADEM.

It is difficult to differentiate the cause of brain abscesses with the use of CT and MR imaging. We did a comparative evaluation of pyogenic, tubercular, and fungal brain abscesses by using conventional, diffusion-weighted imaging (DWI), and proton MR spectroscopy (PMRS) with an aim to define the unique features that may differentiate among the pyogenic, tubercular, and fungal brain abscesses. We performed a retrospective analysis on 110 patients with surgically proved brain abscesses. Imaging studies included T2, T1, postcontrast T1, DWI, and PMRS. Apparent diffusion coefficient (ADC) of the wall and cavity of the abscesses were quantified. The morphologic, physiologic, and metabolite features of pyogenic (n ϭ 91), tubercular (n ϭ 11), and fungal (n ϭ 8) abscesses were compared. The pyogenic abscesses had smooth (55/91) and lobulated (36/91) walls, whereas the tubercular abscesses had smooth (4/11), lobulated (6/11), or crenated walls (1/11) with no intracavitary projections. The fungal abscesses showed irregular walls (lobulated 4/8, crenated 4/8) with intracavitary projections (8/8). The wall as well as the cavity showed low ADC in the pyogenic and tubercular abscesses. In the fungal abscesses, the wall and projections showed low ADC (8/8); however, the cavity itself showed high ADC (8/8). PMRS showed cytosolic amino acids (89/91), acetate (25/91), and succinate (18/91) in the pyogenic abscesses, whereas lipid/lactate (11/11) was seen in the tubercular abscesses. The fungal abscesses showed lipid (4/8), lactate (7/8), amino acids (4/8), and multiple peaks between 3.6 and 3.8 ppm assigned to trehalose (5/8). CONCLUSION: Based on the morphologic, ADC, and metabolite information, it may be possible to differentiate among the pyogenic, tubercular, and fungal brain abscesses.

The impact of induced lipolysis on the composition of plasma lipids is analyzed by proton magnetic resonance spectroscopy (MRS) in humans. The variations of the methylene and methyl resonances from lipids in lipoproteins are studied under two sets of lipolytic conditions: acute endovascular lipolysis induced by an intravenous injection of heparin and subacute lipolysis induced by short fasting. During acute lipolysis, the degradation of the very low density lipoproteins structures is well correlated to the modifications observed in the areas of CH2 and CH3 MRS signals. The comparison of regular spectra, spectra with water signal suppression, and spectra recorded with a spin-echo sequence provides information on the behavior of the different parts of the lipoproteins, that is, the neutral core, little affected by heparine-induced lipoprotein lipase (LPL) activation, and the surface layer supplying substrates to LPL. During 48 h of fasting, only limited modifications occur on the MR spectra, and lipolysis cannot be documented in details.

Localized proton MR spectra of mouse skeletal muscle obtained at 7 T show dipole-dipole coupling effects for creatine and putative taurine resonances and for the lactate methine signal. These effects are independent of the presence of creatine kinase. The intensity of the methylene 1 H resonance of creatine is not different between wild-type and creatine kinase deficient mice, which have a lower phosphocreatine content. 1 H-MR spectra acquired post-mortem from wild-type mouse skeletal muscle parallel to B 0 show a linewidth decrease for the methyl resonance of creatine and a 20% signal intensity loss for its methylene peak concurrent with the total breakdown of phosphocreatine as observed by 31 P-MR spectroscopy. However, with the muscle at the magic angle no changes in the appearance and intensity of creatine (and taurine) resonances are observed. These results indicate that the changes observed for creatine resonances are related to altered dipolar couplings and that the intensity of the methylene peak does not necessarily reflect muscular phosphocreatine content. Magn Reson Med 43:517-524, 2000.

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La principale indication des macrobiopsies sous stéréotaxie est la détection de foyer de microcalcifications. Cette technique est fiable et peut remplacer les biopsies chirurgicales. L'utilisation des biopsies stéréotaxiques est en nette augmentation lors de la découverte de lésions infracliniques en particulier à type de foyers de microcalcifications. La prise en charge des biopsies sous stéréotaxie dans le cadre des prélèvements de microcalcifications est délicate. Le challenge pour le radiologue et le pathologiste est de préserver au maximum de calcifications afin de permettre un diagnostic fiable. Mots clés : macrobiopsies, microcalcifications.

The anterior cingulate cortex (ACC) plays a major role in modulating executive control of attention. Here, 15 medication-naı ¨ve patients with attention deficit/hyperactivity disorder (ADHD) and 10 carefully matched healthy controls were studied with 2D 1 H-magnetic resonance spectroscopic imaging (MRSI) of the ACC [Brodmann areas 24b 0 -c 0 and 32 0 ]. Attentional skills were assessed using the identical pairs version of the continuous performance task (CPT-IP). Analysis of regional brain spectra revealed a significantly increased signal of choline-containing compounds (Ch) in the ACC of ADHD patients (p < 0.05). Across and within groups, the Ch signal showed high correlations with slowed hit reaction times on the CPT-IP. No group differences in N-acetyl-aspartate (NAA) and creatine (tCr) were detectable. The combination of performance deficits and elevated Ch levels in the ACC supports the hypothesis that subtle structural abnormalities underlie the functional alterations in ACC activation previously observed in ADHD patients.