The added value of quantitative multi-voxel MR spectroscopy in breast magnetic resonance imaging.

OBJECTIVE: To determine whether quantitative multivoxel MRS improves the accuracy of MRI in the assessment of breast lesions. METHODS: Twenty-five consecutive patients with 26 breast lesions ≥ 1 cm assessed as BI-RADS 3 or 4 with mammography underwent quantitative multivoxel MRS and contrast-enhanced MRI. The choline (Cho) concentration was calculated using the unsuppressed water signal as a concentration reference. ROC analysis established the diagnostic accuracy of MRI and MRS in the assessment of breast lesions. RESULTS: Respective Cho concentrations in 26 breast lesions re-classified by MRI as BI-RADS 2 (n = 5), 3 (n = 8), 4 (n = 5) and 5 (n = 8) were 1.16 ± 0.43 (mean ± SD), 1.43 ± 0.47, 2.98 ± 2.15 and 4.94 ± 3.10 mM. Two BI-RADS 3 lesions and all BI-RADS 4 and 5 lesions were malignant on histopathology and had Cho concentrations between 1.7 and 11.8 mM (4.03 ± 2.72 SD), which were significantly higher (P = 0.01) than that in the 11 benign lesions (0.4-1.5 mM; 1.19 ± 0.33 SD). Furthermore, Cho concentrations in the benign and malignant breast lesions in BI-RADS 3 category differed (P = 0.01). The accuracy of combined multivoxel MRS/breast MRI BI-RADS re-classification (AUC = 1.00) exceeded that of MRI alone (AUC = 0.96 ± 0.03). CONCLUSIONS: These preliminary data indicate that multivoxel MRS improves the accuracy of MRI when using a Cho concentration cut-off ≤ 1.5 mM for benign lesions. KEY POINTS: Quantitative multivoxel MR spectroscopy can improve the accuracy of contrast-enhanced breast MRI. Multivoxel-MRS can differentiate breast lesions by using the highest Cho-concentration. Multivoxel-MRS can exclude patients with benign breast lesions from further invasive diagnostic procedures.

MR intensity measurements of nondenervated muscle in patients following severe forearm trauma.

Fluid increases resulting in higher MRI signal intensities in T(2) -weighted and short tau inversion recovery (STIR) sequences can be used to diagnose nerve injury. By comparing the signal intensities over time, MRI may become a new method for monitoring the healing process. Muscle edema is assessed by comparing the signal intensity of affected muscle with that of nonaffected muscle. However, in severe forearm trauma, the signal of nondenervated muscle may also be increased by wound edema, thus masking the effect of denervation. Hence, the purpose of this study was to investigate the influence of wound edema on muscle signal intensity in 29 consecutive patients examined on a 1.5-T MRI scanner at 1, 3, 6, 9 and 12 months after severe forearm trauma. The long-term course of wound edema and the influence of wound distance were thus investigated using a standardized imaging, calibration and post-processing protocol. The signal intensities of nondenervated intrinsic hand muscles were measured in the affected and contralateral sides. Muscle signal intensities were increased on the trauma side at 1 and 3 months (18% and 7.4%, respectively; p < 0.001) and normalized thereafter. In the contralateral hand, no significant signal changes were seen. No relationship was found between wound distance and the severity of wound edema. This study shows that wound edema influences muscle signal intensity comparisons in patients with forearm trauma. When comparing denervated muscle with nondenervated muscle, an additional scan of the contralateral side is indicated during the first 6 months after trauma to assess the extent of wound edema. After 6 months, the ipsilateral side can be used for muscle signal intensity comparisons.

Diffusion weighted imaging of the breast: Performance of standardized breast tumor tissue selection methods in clinical decision making.

OBJECTIVES: In breast diffusion weighted imaging (DWI) protocol standardization, it is recently shown that no breast tumor tissue selection (BTTS) method outperformed the others. The purpose of this study is to analyze the feasibility of three fixed-size breast tumor tissue selection (BTTS) methods based on the reproducibility, accuracy and time-measurement in comparison to the largest oval and manual delineation in breast diffusion weighted imaging data. METHODS: This study is performed with a consecutive dataset of 116 breast lesions (98 malignant) of at least 1.0 cm, scanned in accordance with the EUSOBI breast DWI working group recommendations. Reproducibility of the maximum size manual (BTTS1) and of the maximal size round/oval (BTTS2) methods were compared with three smaller fixed-size circular BTTS methods in the middle of each lesion (BTTS3, 0.12 cm3 volume) and at lowest apparent diffusion coefficient (ADC) (BTTS4, 0.12 cm3; BTTS5, 0.24 cm3). Mean ADC values, intraclass-correlation-coefficients (ICCs), area under the curve (AUC) and measurement times (sec) of the 5 BTTS methods were assessed by two observers. RESULTS: Excellent inter- and intra-observer agreement was found for any BTTS (with ICC 0.88-0.92 and 0.92-0.94, respectively). Significant difference in ADCmean between any pair of BTTS methods was shown (p = <0.001-0.009), except for BTTS2 vs. BTTS3 for observer 1 (p = 0.10). AUCs were comparable between BTTS methods, with highest AUC for BTTS2 (0.89-0.91) and lowest for BTTS4 (0.76-0.85). However, as an indicator of clinical feasibility, BTTS2-3 showed shortest measurement times (10-15 sec) compared to BTTS1, 4-5 (19-39 sec). CONCLUSION: The performance of fixed-size BTTS methods, as a potential tool for clinical decision making, shows equal AUC but shorter ADC measurement time compared to manual or oval whole lesion measurements. The advantage of a fixed size BTTS method is the excellent reproducibility. A central fixed breast tumor tissue volume of 0.12 cm3 is the most feasible method for use in clinical practice.

Diagnostic performance of breast tumor tissue selection in diffusion weighted imaging: A systematic review and meta-analysis.

BACKGROUND: Several methods for tumor delineation are used in literature on breast diffusion weighted imaging (DWI) to measure the apparent diffusion coefficient (ADC). However, in the process of reaching consensus on breast DWI scanning protocol, image analysis and interpretation, still no standardized optimal breast tumor tissue selection (BTTS) method exists. Therefore, the purpose of this study is to assess the impact of BTTS methods on ADC in the discrimination of benign from malignant breast lesions in DWI in terms of sensitivity, specificity and area under the curve (AUC). METHODS AND FINDINGS: In this systematic review and meta-analysis, adhering to the PRISMA statement, 61 studies, with 65 study subsets, in females with benign or malignant primary breast lesions (6291 lesions) were assessed. Studies on DWI, quantified by ADC, scanned on 1.5 and 3.0 Tesla and using b-values 0/50 and ≥ 800 s/mm2 were included. PubMed and EMBASE were searched for studies up to 23-10-2019 (n = 2897). Data were pooled based on four BTTS methods (by definition of measured region of interest, ROI): BTTS1: whole breast tumor tissue selection, BTTS2: subtracted whole breast tumor tissue selection, BTTS3: circular breast tumor tissue selection and BTTS4: lowest diffusion breast tumor tissue selection. BTTS methods 2 and 3 excluded necrotic, cystic and hemorrhagic areas. Pooled sensitivity, specificity and AUC of the BTTS methods were calculated. Heterogeneity was explored using the inconsistency index (I2) and considering covariables: field strength, lowest b-value, image of BTTS selection, pre-or post-contrast DWI, slice thickness and ADC threshold. Pooled sensitivity, specificity and AUC were: 0.82 (0.72-0.89), 0.79 (0.65-0.89), 0.88 (0.85-0.90) for BTTS1; 0.91 (0.89-0.93), 0.84 (0.80-0.87), 0.94 (0.91-0.96) for BTTS2; 0.89 (0.86-0.92), 0.90 (0.85-0.93), 0.95 (0.93-0.96) for BTTS3 and 0.90 (0.86-0.93), 0.84 (0.81-0.87), 0.86 (0.82-0.88) for BTTS4, respectively. Significant heterogeneity was found between studies (I2 = 95). CONCLUSIONS: None of the breast tissue selection (BTTS) methodologies outperformed in differentiating benign from malignant breast lesions. The high heterogeneity of ADC data acquisition demands further standardization, such as DWI acquisition parameters and tumor tissue selection to substantially increase the reliability of DWI of the breast.

MR spectroscopy and diffusion tensor imaging of the brain in Sjögren-Larsson syndrome.

Diffusion tensor imaging (DTI) is reported for the first time in a patient with Sjögren-Larsson syndrome, an autosomal recessive neurocutaneous disorder. Magnetic resonance spectroscopy (MRS) revealed normal levels of choline, creatine and N-acetyl aspartate (NAA) and the characteristic lipid signals in the white matter brain tissue. Conventional MRI showed increased signal intensity around the lateral ventricles indicating abnormal myelination. DTI revealed normal apparent diffusion coefficient (ADC) values, but reduced fractional anisotropy (FA) in the white matter. After co-registration of the parameters obtained with DTI with the results of MRS (36 voxels), significant correlations were obtained of lipid content with FA (r=0.81), ADC (r=-0.62), choline (r=0.51), and NAA (r=0.44) (P<0.01, all). These results suggest that in Sjögren-Larsson syndrome, the white matter lipid signals originate from the neurons, with NAA and choline reflecting neuron density and myelination. The comparatively high FA/low ADC values in these lipid-rich locations, indicate a loss of diffusion in directions perpendicular to the fibers. The overall loss of FA in the white matter may reflect a loss of brain tissue water content in SLS patients compared with controls and precede the formation of atrophy.

MR spectroscopy of the brain in Leigh syndrome.

Brain magnetic resonance spectroscopy in two patients with Leigh syndrome revealed the presence of lactate in gray and white matter brain tissue and relatively high choline levels in the white matter. The latter observation, most probably related to an ongoing demyelination process, underlines specific involvement of white matter metabolism in Leigh syndrome even in cases without involvement of the white matter as visualized on MRI. Magnetic resonance spectroscopy might thus be of help in differentiating Leigh syndrome from a range of other mitochondrial diseases, such as ophthalmoplegia and Kearns-Sayre syndrome, showing lack of lactate in brain tissues appearing normal on MRI.

Diffusion tensor imaging and chemical shift imaging assessment of heterogeneity in low grade glioma under temozolomide chemotherapy.

Diffusion tensor imaging and multiple voxel magnetic resonance spectroscopy were performed in the MRI follow-up of a patient with a glioma treated with temozolomide chemotherapy. Tumor shrinkage was paralleled by reductions in choline level and by increases in apparent diffusion coefficient indicating decreased cellularity. Within the tumor, choline level and apparent diffusion coefficient showed a significant inverse correlation (P < 0.01). Fractional anisotropy distribution in the tumor correlated positively with N-acetyl aspartate level (P < 0.001), indicating that these parameters reflect (remaining) axonal structure. Tumor lactate level, also found to decrease under therapy, did not correlate with any other parameter.

MR spectroscopy and diffusion tensor imaging of the brain in congenital muscular dystrophy with merosin deficiency: metabolite level decreases, fractional anisotropy decreases, and apparent diffusion coefficient increases in the white matter.

Brain magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) in one patient with merosin-deficient congenital muscular dystrophy (MDCMD) revealed significant metabolite (choline, creatine, N-acetyl aspartate) level reductions, fractional anisotropy (FA) reduction and increased apparent diffusion coefficient (ADC) in the white matter (p<0.01, all). In the gray matter, the MRS properties did not differ significantly from those in controls. The ADC and FA, however, differed significantly as in the white matter, although the differences were less pronounced. This is the first quantitative MR study of the brain in a patient with MDCMD, which revealed that the concentrations of all MRS measured metabolites were decreased only in the white matter. This observation, combined with the DTI observed ADC increases and FA decrease, indicated a presence of vasogenic edema in the white matter.

19F magnetic resonance spectroscopy studies of the metabolism of 5-fluorouracil in murine RIF-1 tumors and liver.

The metabolism of 5-fluorouracil (5FU) in tumors and livers of RIF-1 tumor-bearing C3H mice given i.p. injections of 5FU was serially monitored by 19F magnetic resonance spectroscopy. The levels of 5FU and fluoronucleotide detected in the tumors after a dose of 130 mg/kg (n = 13) were less than one-third of those after 260-mg/kg 5FU (n = 14). During the days after these doses, tumor size decreased by 24 +/- 3 and 52 +/- 6 SEM%, respectively. A second 130-mg/kg dose, given at day 7 after the first 130-mg/kg dose, resulted in still lower tumor fluorine levels and little change in tumor size. There was a significant correlation between the magnetic resonance spectroscopy-detected fluoronucleotide levels and the shrinkage of tumors after the 260-mg/kg dose (r = 0.44; P = 0.024). In mouse liver, the degradation of 5FU to alpha-fluoro-beta-ureidoprobionic acid and alpha-fluoro-beta-alanine after the 260-mg dose (n = 13) was slower than after a dose of 130 mg/kg (n = 14). For the respective doses, the half-life of 5FU was 59 +/- 7 versus 28 +/- 2 SEM min (P less than 0.0001). There was a negative correlation between the levels of 5FU catabolite (alpha-fluoro-beta-ureidoprobionic acid and alpha-fluoro-beta-alanine) in liver and fluoronucleotide in tumor (r = -0.80; P = 0.0020), which indicates that the degradation in liver and the activation of 5FU in tumor are competing processes.

In vivo 31P-nuclear magnetic resonance study of the response of a murine mammary tumor to different doses of gamma-radiation.

The response of the s.c. implanted murine mammary carcinoma NU-82 to 10 and 20 Gy of gamma-radiation was followed by in vivo 31P-nuclear magnetic resonance spectroscopy on 48 mice during a period of 2 days. During the first 8 h after a dose of 10 Gy, the ratio of ATP/inorganic phosphate increases to a value of 120 +/- 15% (SE) of the control value. This rise is followed by a decrease of the ratio to 74 +/- 12% after 47 h. However treatment with 20 Gy causes the ratio of ATP/Pi to decrease gradually to a level of 45 +/- 7% after 47 h. Histological investigations demonstrated that radiation-induced necrosis largely contributes to this phenomenon. During the time of observation irradiated tumors displayed no changes in size and intracellular pH. After treatment with 10 Gy as well as with 20 Gy, the phosphodiester resonance decreased in intensity. By 31P-nuclear magnetic resonance spectroscopy on extracts of the NU-82 tumor, two phosphodiesters were identified, glycerophosphocholine and glycerophosphoethanolamine.

Murine mammary tumor response to hyperthermia and radiotherapy evaluated by in vivo 31P-nuclear magnetic resonance spectroscopy.

The response of the s.c.-implanted murine mammary carcinoma NU-82 to hyperthermia was followed as a function of time by 31P-nuclear magnetic resonance spectroscopy. Treatment consisted of elevation of the temperature of the tumors to 41-45 degrees C during 15 min. At 18 h after temperatures of up to 42, 43, 44, and 45 degrees C the ratio of ATP/Pi was unchanged, decreased, largely decreased, and approaching zero, respectively. After the higher doses the relative concentrations (in percentage of total phosphate as visible in the nuclear magnetic resonance spectrum) of phosphomonoesters (mainly phosphoethanolamine) and phosphocreatine also decreased in favor of Pi. The changes in phosphodiesters (mainly glycerophosphocholine) correlated linearly with the changes in ATP (r = 0.84, P less than 0.025). Whereas the limited spectral changes after a dose of 43 degrees C were nullified within 24 h, the more drastic changes after a dose of 45 degrees C lasted at least 8 days. The heavier dose not only induced temporary decreases in tumor perfusion like the lower dose (phase 1) but subsequently, unlike the lower dose, resulted in formation of necrosis (phase 2). In the same tumor we found increases in Pi and decreases in ATP and phosphodiesters after radiotherapy with a dose of 20 Gy. Radiotherapy (20 Gy) combined with hyperthermia (44 degrees C) appeared to strengthen these effects and resulted in an improved tumor response (regression).

Altered hepatic gluconeogenesis during L-alanine infusion in weight-losing lung cancer patients as observed by phosphorus magnetic resonance spectroscopy and turnover measurements.

Profound alterations in host metabolism in lung cancer patients with weight loss have been reported, including elevated phosphomonoesters (PMEs) as detected by 31P magnetic resonance spectroscopy (MRS). In healthy subjects, infusion of L-alanine induced significant increases in hepatic PMEs and phosphodiesters (PDEs) due to rising concentrations of 3-phosphoglycerate and phosphoenolpyruvate, respectively. The aim of the present study was to monitor these changes in the tumor-free liver of lung cancer patients during L-alanine infusion by means of simultaneous 31P MRS and turnover measurements. Twenty-one lung cancer patients without liver metastases with (CaWL) or without weight loss (CaWS), and 12 healthy control subjects were studied during an i.v. L-alanine challenge of 1.4-2.8 mmol/kg followed by 2.8 mmol/kg/h for 90 min. Plasma L-alanine concentrations increased during alanine infusion, from 0.35-0.37 mM at baseline to 5.37 +/- 0.14 mM in the CaWL patients, 6.67 +/- 0.51 mM in the CaWS patients, and 8.47 +/- 0.88 mM in the controls (difference from baseline and between groups during alanine infusion, all P < 0.001). Glucose turnover and liver PME levels at baseline were significantly elevated in the CaWL patients. Alanine infusion increased whole-body glucose turnover by 8 +/- 3% in the CaWS patients (P = 0.03), whereas no significant change occurred in the CaWL and controls. PME levels increased by 50 +/- 16% in controls (area under the curve, P < 0.01) and by 87 +/- 31% in the CaWS patients (P < 0.05) after 45-90 min. In contrast, no significant changes in PME levels were observed in the CaWL patients. Plasma insulin concentrations increased during L-alanine infusion in all groups to levels that were lower in the CaWL patients than in the CaWS patients and controls (P < 0.05). In lung cancer patients, but not in controls, changes in PME and PDE levels during alanine infusion were inversely correlated with their respective baseline levels (r = -0.82 and -0.86, respectively; P < 0.001). In addition, changes in PMEs during alanine infusion in lung cancer patients were inversely correlated with the degree of weight loss (r = -0.54; P < 0.05). This study demonstrates the presence of major alterations in the pathway of hepatic gluconeogenesis in weight-losing lung cancer patients, as shown by elevated glucose flux before and during L-alanine infusion, and by the increased PME and PDE levels, which reflect accumulation of gluconeogenic intermediates in these patients. Weight-stable lung cancer patients show accelerated increases in PME and PDE levels during L-alanine infusion, suggesting enhanced induction of the gluconeogenic pathway. Our results suggest altered gluconeogenic enzyme activities and elevated alanine uptake within the livers of weight-losing/weight-stable lung cancer patients.

Quantitative Myocardial Perfusion with Dynamic Contrast-Enhanced Imaging in MRI and CT: Theoretical Models and Current Implementation.

Technological advances in magnetic resonance imaging (MRI) and computed tomography (CT), including higher spatial and temporal resolution, have made the prospect of performing absolute myocardial perfusion quantification possible, previously only achievable with positron emission tomography (PET). This could facilitate integration of myocardial perfusion biomarkers into the current workup for coronary artery disease (CAD), as MRI and CT systems are more widely available than PET scanners. Cardiac PET scanning remains expensive and is restricted by the requirement of a nearby cyclotron. Clinical evidence is needed to demonstrate that MRI and CT have similar accuracy for myocardial perfusion quantification as PET. However, lack of standardization of acquisition protocols and tracer kinetic model selection complicates comparison between different studies and modalities. The aim of this overview is to provide insight into the different tracer kinetic models for quantitative myocardial perfusion analysis and to address typical implementation issues in MRI and CT. We compare different models based on their theoretical derivations and present the respective consequences for MRI and CT acquisition parameters, highlighting the interplay between tracer kinetic modeling and acquisition settings.

Rapid ELISA assay for plasma D-dimer in the diagnosis of segmental and subsegmental pulmonary embolism. A comparison with pulmonary angiography.

STUDY OBJECTIVE: To assess the accuracy of a rapid ELISA D-dimer assay for the exclusion of pulmonary embolism (PE) in patients suspected of PE, using pulmonary angiography alone as reference method rather than a diagnostic strategy including lung scintigraphy and leg vein ultrasonography. METHODS: In 342 patients who were examined by pulmonary angiography to diagnose or exclude PE, the accuracy of the quantitative rapid VIDAS D-dimer test for the exclusion of PE was evaluated retrospectively. D-dimer levels were assayed in frozen samples collected during the diagnostic work-up at the time of pulmonary angiography while on treatment with unfractionated heparin for 1-2 days. RESULTS: Mean plasma D-dimer concentrations were increased in patients with angiographic evidence of PE (P <0.0001). The sensitivity of D-dimer for segmental PE was 98%, its accuracy in excluding segmental PE was 99%, higher than the respective figures for subsegmental PE (76% and 94%; P <0.01, both). For both forms of PE combined the sensitivity was 90% and the negative predictive value 94%. DISCUSSION: The sensitivity and negative predictive values reported here, are low compared with previous studies using the same rapid ELISA D-dimer assay. This probably reflects an overlooking of mild cases of subsegmental PE in previous studies, although a reduction of D-dimer levels by the heparin pretreatment may have contributed to part of the discrepancy. Prospective studies are needed to clarify this issue.

31P magnetic resonance spectroscopy detection of response-predictive adenosine triphosphate decrease in irradiated radiation-induced fibrosarcoma-1 tumors.

RATIONALE AND OBJECTIVES: In previous phosphorus-31 (31P) magnetic resonance (MR) spectroscopy studies of radiation-induced fibrosarcoma (RIF-1), tumor model single-dose x-ray irradiation was applied at subcurative doses. A more effective x-ray does was used in this study, allowing correlation of treatment efficacy with the early changes observed in the 31P MR spectra of RIF-1 tumors. METHODS: Subcutaneous RIF-1 tumors of 60 mice were examined by 31P MR spectroscopy shortly before a single localized x-ray dose of 40 Gy and at eight times (2, 12, 24, 48, 72, 120, 168, and 216 hours) thereafter. RESULTS: Early increases in the relative concentration of inorganic phosphate and decreases in adenosine triphosphate (ATP), most notably at 2 and 12 hours (each P < 0.00001), were observed that lasted up to 48 hours after irradiation. Phosphomonoester and tumor pH showed decreases that reversed even earlier. Reduction of ATP measured at 48 hours after irradiation was, however, correlated with percent tumor shrinkage observed during the subsequent weeks (r = -0.59; P < 0.00001). CONCLUSIONS: Sustained loss of RIF-1 tumor ATP is predictive of treatment efficacy. Temporary depression of high-energy phosphate in favor of inorganic phosphate does not necessarily lead to cell death.

Phosphorus-31 chemical shift imaging of metastatic tumors located in the spine region.

RATIONALE AND OBJECTIVES: Phosphorus-31 magnetic resonance spectroscopy was used in 14 cases to examine metastases of known malignant tumors located in the spine region. The purpose was to test the hypothesis that tumor phosphomonoester (PME) is elevated. METHODS: Two-dimensional chemical shift imaging was used in combination with a slice-select gradient in the third dimension to obtain true three-dimensional localization. RESULTS: The spectral maps revealed PME signals increased up to 10 times in voxels containing contrast-enhancing metastatic spine lesions compared with adjacent areas and peripheral muscle voxels. Phosphomonoester increase was significant for all tumors combined (8.6 +/- 5.3 arbitrary units versus 2.4 +/- 0.5 and 2.2 +/- 0.8 arbitrary units in unaffected myelum and corpora; P < 0.001), though smaller than 2 standard deviations in 5 of 14 cases. The latter shared high proportions of phosphocreatine, phosphocreatine > 30% of total phosphate, indicating substantial amounts of muscle tissue included in the tumor voxels (partial volume effect). CONCLUSIONS: Phosphorus-31 MR spectroscopy can be of value in the recognition of malignant vertebral column abnormalities. Malignant tumor is marked by drastic PME increases-fourfold to tenfold, provided that partial volume effects are small.

Safety and efficacy of dotarem (Gd-DOTA) versus magnevist (Gd-DTPA) in magnetic resonance imaging of the central nervous system.

RATIONALE AND OBJECTIVES: Gd-DTPA is a well-characterized, safe contrast agent frequently used in magnetic resonance imaging (MRI) of the central nervous system. The purpose of this double-blind, comparative MRI study of brain, spine, trunk, and limbs was to evaluate the safety and efficacy of Gd-DOTA versus Gd-DTPA in a large number of patients (n = 1038). METHODS: T1-weighted MRI was performed before contrast and after the administration of Gd-DOTA or Gd-DTPA (0.1 mmol/kg). The MR images were scored for image quality, and the diagnostic efficacy also was assessed. Patients were questioned 1 hour after injection, and adverse reactions were recorded. RESULTS: Image quality of the T1-weighted MR images without contrast was good or excellent in 89.7% and 91.7% of the Gd-DOTA and Gd-DTPA groups, respectively (P > 0.2). After contrast, 85.8% (Gd-DOTA) and 88.2% (Gd-DTPA) of the T1-weighted MR images were of good to excellent image quality (P > 0.2), significantly less than before contrast (P < 0.001, both groups). In 82.3% of the Gd-DOTA group and 83.5% of the Gd-DTPA group (P > 0.2), the information obtained was more accurate with the administration of contrast agents. In 82.4% (Gd-DTPA) and 81.9% (Gd-DOTA) of patients, confirmation was obtained of diagnosis without contrast, whereas in 17.0% and 17.3% of patients, therapy was modified as a result of the use of contrast (P > 0.2, both groups). The MRI investigation was reported as abnormal in 58.3% (Gd-DOTA) and 59.6% of patients (Gd-DTPA), indicating a similar prevalence of disease in each group. Patients responded that 97.8% (Gd-DOTA) and 98.5% (Gd-DTPA) of the investigations went well and adverse reactions, none of them serious, were encountered in 0.97% of Gd-DOTA and 0.77% of Gd-DTPA groups (P > 0.2, both groups). CONCLUSION: This double-blind, randomized, clinical trial comparing Gd-DTPA and Gd-DOTA revealed no serious adverse reactions, whereas minor adverse reactions were encountered in fewer than 1% of patients. Gd-DOTA is as safe a contrast agent as Gd-DTPA and has similar diagnostic efficacy.

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 OBJECTIVES: The 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. METHODS: Thirteen 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. RESULTS: Follow-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). CONCLUSIONS: The 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).

Human brain chemical shift imaging at age 60 to 90: analysis of the causes of the observed sex differences in brain metabolites.

RATIONALE AND OBJECTIVES: To assess whether differences in cerebral atrophy and white matter lesions or in the presence of lactate and lipid signals can explain the observed differences in brain choline, creatine, and N-acetylaspartate levels between healthy elderly women and men. METHODS: In addition to standard magnetic resonance imaging of the brain, an 8 x 8 x 2-cm3 supraventricular transverse brain volume parallel to the canthomeatal line was examined by magnetic resonance spectroscopy (automated 1H chemical shift imaging) in 540 healthy elderly persons. RESULTS: At P = 0.01, 0.001, and 0.0001, choline differed between women and men in 14, 9, and 5 of 36 voxels, respectively. On correction for cerebral atrophy (more frequent in men than in women), white matter lesions (more frequent in women), and lactate and lipid (more frequent in women), the differences in choline were reduced to 13, 6, and 3. Sex differences for creatine and N-acetylaspartate were similar but less numerous after correction. CONCLUSIONS: Elderly women and men in the general population show differences in the levels of creatine, N-acetylaspartate, and especially choline in portions of the brain. The sex-related differences in brain metabolite levels cannot be explained by differences in cerebral atrophy or other aging-related phenomena (white matter lesions, lactate, lipid).

Thymidine-modulated 5-fluorouracil metabolism in liver and RIF-1 tumors studied by 19F magnetic resonance spectroscopy.

19F Magnetic resonance spectroscopy was used to study the impact of the biochemical modulator thymidine (TdR) on the 5-fluorouracil (5FU) metabolism in the livers and radiation-induced fibrosarcoma (RIF-1) tumors of 5FU-treated C3H mice. The liver spectra measured after administration of 5FU (65 or 130 mg/kg IP) showed the 5 FU resonance and its catabolites alpha-fluoro-beta-ureidopropionic acid and alpha-fluoro-beta-alanine. At the latter dose, fluoronucleotide signal was also detected. The liver spectra of TdR-pretreated (500 mg/kg, IP) mice showed additional signals of fluoronucleotide and fluoronucleoside at both 5FU doses, while alpha-fluoro-beta-alanine was not detected. TdR pretreatment increased the half-life of 5FU in livers from 24 +/- 2 to 126 +/- 46 SEM min at the 5FU dose of 65 mg/kg and from 28 +/- 2 to 95 +/- 22 min at the 130 mg/kg dose (P less than .1 and P less than .01, respectively). TdR-pretreated mice had higher 5FU anabolite (fluoronucleotide + fluoronucleoside) levels in their RIF-1 tumors than nonpretreated mice that received the same 5FU doses (56 +/- 15 SEM vs. 0 arbitrary units at the 5FU dose of 65 mg/kg, and 88 +/- 21 vs. 10 +/- 3 arbitrary units at 130 mg/kg 5FU; P less than .0001). The percentage drop in tumor volume was enhanced in the mice that received TdR, from 27 +/- 4 SEM to 52 +/- 2 at the 5 FU dose of 65 mg/kg and from 24 +/- 3 to 65 +/- 4 at the 130-mg/kg dose (P less than .0001, both).