Paul E. Sijens

1H MR Spectroscopy Detection of Lipids and Lactate in Metastatic Brain Tumors

1H MR spectroscopy was used to correlate the metabolite signals in 66 untreated metastatic brain tumors with the results of Gd‐DTPA enhanced MRI. Cubic volumes containing brain metastases of lung cancer (n=17), mammary carcinoma (n=24), melanoma (n=12) and those originating from other tumors (n=13) were examined using the double spin echo technique with CHESS pulses for water suppression and TE=135 ms. Apart from trends toward reduced signals of choline‐containing compounds (Cho) and reduced post‐Gd MRI contrast in lung cancer compared with the other pathology groups, the four tumor groups had similar MRI and MRS characteristics. Metastases without lipid or lactate (Lact) signal in the 1H MR spectra were comparatively small in size with homogeneous post‐Gd MRI enhancement (33±5%, means±SEM; n=24) and elevated Cho signals compared with normal contralateral brain tissue (70±5% of contralateral N‐acetyl aspartate signal; p<0.001). The other metastases showed either unambiguous lipid signals (n=30) or MRS detectable Lact (n=12) and were heterogeneous on MRI with divergent signals of Gd‐enhancement (49±5% vs 14±8%, p<0.001) and Cho (88±10 vs 47±8% of contralateral NAA; p=0.02). Those with Lact were significantly larger compared with both other groups (p<0.02, both). It is concluded that brain metastases can be categorized into early stage (Cho), intermediate stage (lipid, higher Cho) and late stage metastases (Lact, lower Cho).

Diffusion-weighted imaging of normal fibroglandular breast tissue: influence of microperfusion and fat suppression technique on the apparent diffusion coefficient.

The influence of microperfusion and fat suppression technique on the apparent diffusion coefficient (ADC) values obtained with diffusion weighted imaging (DWI) of normal fibroglandular breast tissue was investigated. Seven volunteers (14 breasts) were scanned using diffusion weighting factors (b values) up to 1600 s/mm2 and the four different fat suppression techniques: STIR, fat saturation, SPAIR, and Water Excitation. The relationship between the logarithmic DW attenuation curves and b was linear for b values up to 600 s/mm2 (R2 > 0.999). Small differences were noted between the ADC values obtained with the various fat suppression methods, especially at the higher b values. Water Excitation had the highest mean SNR, exceeding STIR (p = 0.03) though not significantly different from fat saturation and SPAIR. In conclusion, the ADC of fibroglandular breast tissue is not influenced by microperfusion and Water Excitation is recommended because it yielded the best SNR values. These factors may be crucial in the differentiation between benign and malignant lesions. Copyright

Inverse association between liver fat content and hepatic glucose uptake in patients with type 2 diabetes mellitus

The objective of this research was to study (1) the mutual relationship between liver fat content (LFC) and hepatic glucose uptake (HGU) in patients with type 2 diabetes mellitus and (2) the relationship between changes in LFC and HGU uptake induced by rosiglitazone in these patients. Liver fat was measured with proton magnetic resonance spectroscopy and insulin-stimulated HGU with [(18)F]-labeled 2-fluoro-2-deoxyglucose positron emission tomography in 54 patients with type 2 diabetes mellitus and 8 healthy subjects. Measurements were repeated in diabetic patients after a 16-week intervention period with rosiglitazone (n = 27) or placebo (n = 27). Patients with diabetes had lower HGU (24.5 +/- 14.2 vs 35.6 +/- 9.7 micromol/[kg min], P < .01) and higher LFC (10.9% +/- 9.2% vs 2.5% +/- 1.4%, P < .001) compared with healthy subjects. Liver fat was inversely associated with HGU (r = -0.31, P < .05), but more strongly with whole-body insulin sensitivity and adiponectin levels. Rosiglitazone treatment reduced liver fat by 24.8% (P = .01 vs placebo) and increased HGU by 29.2% (P = .013 vs placebo). This decrease in LFC was best explained by the increment in suppression of nonesterified fatty acid levels during hyperinsulinemia (P < .001) and improved glycemic control (P = .034), but not by changes in HGU. A significant inverse relationship between LFC and HGU was observed, but changes were not related. This suggests that the beneficial effects of rosiglitazone on liver metabolism are indirect and can be partly explained by increased suppression of nonesterified fatty acid levels, leading to reduced liver fat.

Assessment of the variations in fat content in normal liver using a fast MR imaging method in comparison with results obtained by spectroscopic imaging

A recently published Dixon-based MRI method for quantifying liver fat content using dual-echo breath-hold gradient echo imaging was validated by phantom experiments and compared with results of biopsy in two patients (Radiology 2005;237:1048-1055). We applied this method in ten healthy volunteers and compared the outcomes with the results of MR spectroscopy (MRS), the gold standard in quantifying liver fat content. Novel was the use of spectroscopic imaging yielding the variations in fat content across the liver rather than a single value obtained by single voxel MRS. Compared with the results of MRS, liver fat content according to MRI was too high in nine subjects (range 3.3–10.7% vs. 0.9–7.7%) and correct in one (21.1 vs. 21.3%). Furthermore, in one of the ten subjects the MRI fat content according to the Dixon-based MRI method was incorrect due to a (100-x) versus x percent lipid content mix-up. The second problem was fixed by a minor adjustment of the MRI algorithm. Despite systematic overestimation of liver fat contents by MRI, Spearman’s correlation between the adjusted MRI liver fat contents with MRS was high (r = 0.927, P < 0.001). Even after correction of the algorithm, the problem remaining with the Dixon-based MRI method for the assessment of liver fat content,is that, at the lower end range, liver fat content is systematically overestimated by 4%.

1H MR spectroscopy monitoring of changes in choline peak area and line shape after Gd-contrast administration

Fifteen percent loss in the peak area of choline containing compounds (Cho) was recently observed in 1H MR spectra of contrast-enhancing tumor at 5-10 min after Gd-contrast administration [Magn. Reson. Med. 37:222-225, 1997]. In this study, chemical shift imaging (CSI, 1500/135 ms PRESS) was used to assess the spectral changes in 47 Gd-enhancing glial brain tumors and metastatic brain tumors measured at 0-5, 5-10, and/or 10-15 min after administration of Gd-contrast. Percent Cho peak area losses measured at these times, 3 +/- 3, 12 +/- 2, and 14 +/- 3 SEM, respectively, coincided with trends of line narrowing and up-field shift of the Cho peak. Significant changes in creatine and N-acetyl acetate signals were not observed. It is concluded that the Gd-induced loss of tumor Cho signal measured after 5 min, typically required for post contrast-MRI and the positioning of the CSI volume on tumor, shows little further change with time, if any.

Impact of fluoxetine on the human brain in multiple sclerosis as quantified by proton magnetic resonance spectroscopy and diffusion tensor imaging

The antidepressant fluoxetine stimulates astrocytic glycogenolysis, which serves as an energy source for axons. In multiple sclerosis patients fluoxetine administration may improve energy supply in neuron cells and thus inhibit axonal degeneration. In a preliminary pilot study, 15 patients with multiple sclerosis (MS) were examined by diffusion tensor imaging (DTI) and (1)H magnetic resonance spectroscopy (MRS) in order to quantify the brain tissue diffusion properties (fractional anisotropy, apparent diffusion coefficient) and metabolite levels (choline, creatine and N-acetylaspartate) in cortical gray matter brain tissue, in normal appearing white matter and in white matter lesions. After oral administration of fluoxetine (20 mg/day) for 1 week, the DTI and MRS measurements were repeated and after treatment with a higher dose (40 mg/day) during the next week, a third series of DTI/MRS examinations was performed in order to assess any changes in diffusion properties and metabolism. One trend was observed in gray matter tissue, a decrease of choline measured at weeks 1 and 2 (significant in a subgroup of 11 relapsing remitting/secondary progressive MS patients). In white matter lesions, the apparent diffusion coefficient was increased at week 1 and N-acetylaspartate was increased at week 2 (both significant). These preliminary results provide evidence of a neuroprotective effect of fluoxetine in MS by the observed partial normalization of the structure-related MRS parameter N-acetylaspartate in white matter lesions.

1H magnetic resonance spectroscopy in monocarboxylate transporter 8 gene deficiency.

CONTEXT In monocarboxylate transporter 8 (MCT8) gene deficiency, a syndrome combining thyroid and neurological abnormalities, the central nervous system has not yet been characterized by magnetic resonance (MR) spectroscopy. OBJECTIVE We studied whether the degree of dysmyelinization in MCT8 gene deficiency according to MR imaging (MRI) is coupled with abnormalities in brain metabolism. DESIGN MRI and MR spectroscopy of the brain were performed twice in two MCT8 gene deficiency patients, for the first time at age 8-10 months and for the second time at age 17-28 months. The results were compared with those obtained in controls of a similar age. RESULTS Compared with controls, young children with MCT8 show choline and myoinositol level increases and N-acetyl aspartate decreases in supraventricular gray and white matter, phenomena associated with the degree of dysmyelinization according to MRI. CONCLUSION MCT8 gene deficiency results in deviant myelinization and general atrophy, which is substantiated by the MR spectroscopy findings of increased choline and myoinositol levels and decreased N-acetyl aspartate. The observations suggest that different mutations in the MCT8 gene lead to differences in the severity of the clinical spectrum, dysmyelinization, and MR spectroscopy-detectable changes in brain metabolism.

Understanding the Discrepancies Between 31P MR Spectroscopy Assessed Liver Metabolite Concentrations from Different Institutions

The high divergence between the liver metabolite concentrations and pH values reported in previous quantitative 31P magnetic resonance studies, for instance phosphomonoester (0.7-3.8 mM) and phosphodiester (3.5-9.7 mM), has not been addressed in the literature. To assess what level of discrepancy can be caused by processing and metabolite integration, in this study chemical shift imaging localized 31P magnetic resonance spectra of human liver were quantitated by three methods currently applied in clinical practice: peak areas defined manually by placement of two cursors vs. frequency domain curve fitting with the assumption of either Gaussian or Lorentzian line shapes. Large reproducible differences were found in liver metabolite peak areas but not in pH, indicating that processing and peak integration methods can only explain part of the discrepancies between the results from different institutions.

Fluoxetine increases cerebral white matter NAA/Cr ratio in patients with multiple sclerosis

Axonal degeneration in multiple sclerosis (MS) may be caused by mitochondrial dysfunction and is associated with decreased levels of N-acetylaspartate (NAA) as measured with 1H-magnetic resonance spectroscopy (MRS). Fluoxetine stimulates astrocytic glycogenolysis, which serves as an energy source for axons. Eleven patients with MS received fluoxetine orally 20 mg a day during the first week, and 40 mg a day during the second week. The mean NAA/Creatine ratio in cerebral white matter of the MS patients increased from 1.77 at baseline to 1.84 at the end of the second week (p=0.007). These findings show evidence for a reversible axonal dysfunction in patients with MS and provide a rationale for investigating whether fluoxetine has neuroprotective effects in MS.

Hydrogen magnetic resonance spectroscopy follow-up after radiation therapy of human brain cancer: Unexpected inverse correlation between the changes in tumor choline level and post-gadolinium magnetic resonance imaging contrast

RATIONALE AND OBJECTIVESThe anatomic and metabolic changes in human brain tumors treated by radiation therapy were compared using gadolinium-enhanced magnetic resonance imaging and hydrogen (1H) magnetic resonance spectroscopy. The study was intended to assess the potential of 1H magnetic resonance spectroscopy in monitoring response to therapy. METHODSThirteen cases of brain cancer treated by radiation therapy were examined by 1H magnetic resonance spectroscopy and gadolinium-enhanced T1-weighted magnetic resonance imaging and reexamined at 2-month intervals. RESULTSFollow-up after radiation therapy showed changes in post-gadolinium magnetic resonance imaging contrast that are inversely correlated with the changes in choline level (r = –0.69, P < 0.00001) and in tumor volume (r = –0.35, P < 0.05). CONCLUSIONSThe choline loss in tumors gaining post-gadolinium magnetic resonance imaging contrast after therapy is unexpected in view of previously reported correlation between the two in untreated metastatic brain tumors. Indicated is the use of 1H magnetic resonance spectroscopy to discriminate enhancing brain tumors with a high content of vital tumor cells (high choline) from tumors, combining decreased cell density with increased interstitial space (low choline).