Andreas Stadlbauer

Diffusion-weighted MR for Differentiation of Breast Lesions at 3.0 T: How Does Selection of Diffusion Protocols Affect Diagnosis?

PURPOSE To compare the diagnostic quality of diffusion-weighted (DW) imaging schemes with regard to apparent diffusion coefficient (ADC) accuracy, ADC precision, and DW imaging contrast-to-noise ratio (CNR) for different types of lesions and breast tissue. MATERIALS AND METHODS Institutional review board approval and written, informed consent were obtained. Fifty-one patients with histopathologic correlation or follow-up performed with a 3.0-T MR imager were included in this study. There were 112 regions of interest drawn in 24 malignant, 17 benign, 20 cystic, and 51 normal tissue regions. ADC maps were calculated for combinations of 10 b values (range, 0-1250 sec/mm(2)). Differences in ADC among tissue types were evaluated. The CNRs of lesions at DW imaging were compared for all b values. A repeated-measures analysis of variance was used to assess lesion differentiation. RESULTS ADCs calculated from b values of 50 and 850 sec/mm(2) were 0.99 x 10(-3) mm(2)/sec +/- 0.18 (standard deviation), 1.47 x 10(-3) mm(2)/sec +/- 0.21, 1.85 x 10(-3) mm(2)/sec +/- 0.22, and 2.64 x 10(-3) mm(2)/sec +/- 0.30 for malignant, benign, normal, and cystic tissues, respectively. An ADC threshold level of 1.25 x 10(-3) mm(2)/sec allowed discrimination between malignant and benign lesions with a diagnostic accuracy of 95% (P < .001). ADC calculations performed with multiple b values were not significantly more precise than those performed with only two. We found an overestimation of ADC for maximum b values of up to 1000 sec/mm(2). The best CNR for tumors was identified at 850 sec/mm(2). CONCLUSION Optimum ADC determination and DW imaging quality at 3.0 T was found with a combined b value protocol of 50 and 850 sec/mm(2). This provided a high accuracy for differentiation of benign and malignant breast tumors.

Quantification of metabolic differences in the frontal brain of depressive patients and controls obtained by 1H-MRS at 3 Tesla.

Rationale and ObjectivesThis study compared metabolic differences in the frontal brain of depressed patients versus age- and sex-matched controls using proton magnetic resonance spectroscopy and absolute quantification of metabolites (NAA, Cr, Cho, mI) at 3 Tesla. MethodsShort-echo-time stimulated echo acquisition mode (TE/TM/TR=20/30/6000 milliseconds) was applied in the prefrontal region of 17 depressed patients and 17 age- and sex-matched controls. Metabolic ratios, ie, N-acetyl-aspartate/creatine (Cr), choline/Cr, and myo-inositol/Cr, and absolute concentrations (using internal water as a reference together with LCModel-based spectra fitting) were calculated and compared between groups and published reference data. ResultsMetabolic ratios showed significantly lower N-acetyl-aspartate/Cr (P = 0.016/0.006, left/right), choline/Cr (P = n.s./0.016), and myo-inositol/Cr (P = 0.022/0.026) for depressive patients versus controls. However, depressive patients showed significantly higher absolute concentrations of Cr (P = 0.017/0.0004) compared with controls with no differences in all other metabolites estimated. ConclusionsThe authors demonstrate that absolute quantification of metabolite concentration is essential in properly identifying pathologic differences of brain metabolites in depression.

Improved delineation of brain tumors: an automated method for segmentation based on pathologic changes of 1H-MRSI metabolites in gliomas

In this study, we developed a method to improve the delineation of intrinsic brain tumors based on the changes in metabolism due to tumor infiltration. Proton magnetic resonance spectroscopic imaging ((1)H-MRSI) with a nominal voxel size of 0.45 cm(3) was used to investigate the spatial distribution of choline-containing compounds (Cho), creatine (Cr) and N-acetyl-aspartate (NAA) in brain tumors and normal brain. Ten patients with untreated gliomas were examined on a 1.5 T clinical scanner using a MRSI sequence with PRESS volume preselection. Metabolic maps of Cho, Cr, NAA and Cho/NAA ratios were calculated. Tumors were automatically segmented in the Cho/NAA images based on the assumption of Gaussian distribution of Cho/NAA values in normal brain using a limit for normal brain tissue of the mean + three times the standard deviation. Based on this threshold, an area was calculated which was delineated as pathologic tissue. This area was then compared to areas of hyperintense signal caused by the tumor in T2-weighted MRI, which were determined by a region growing algorithm in combination with visual inspection by two experienced clinicians. The area that was abnormal on (1)H-MRSI exceeded the area delineated via T2 signal changes in the tumor (mean difference 24%) in all cases. For verification of higher sensitivity of our spectroscopic imaging strategy we developed a method for coregistration of MRI and MRSI data sets. Integration of the biochemical information into a frameless stereotactic system allowed biopsy sampling from the brain areas that showed normal T2-weighted signal but abnormal (1)H-MRSI changes. The histological findings showed tumor infiltration ranging from about 4-17% in areas differentiated from normal tissue by (1)H-MRSI only. We conclude that high spatial resolution (1)H-MRSI (nominal voxel size = 0.45 cm(3)) in combination with our segmentation algorithm can improve delineation of tumor borders compared to routine MRI tumor diagnosis.

Diffusion tensor imaging and optimized fiber tracking in glioma patients: Histopathologic evaluation of tumor-invaded white matter structures

Fiber tracking is increasingly used to plan and guide neurosurgical procedures of intracranial tumors in the vicinity of functionally important areas of the brain. However, valid data concerning the reliability of tracking with respect to the actual pathoanatomical situation are lacking. We retrospectively correlated fiber tracking based on magnetic resonance (MR) DT imaging with the histopathological data of 25 patients with WHO grade II and III gliomas. Fiber tracking using the Fiber Assignment by Continuous Tracking (FACT) method was performed to investigate the integrity of white matter tracts in the surrounding border zone of the lesions. The tracking procedure was stopped when fractional anisotropy (FA) thresholds = 0.1, 0.15, 0.2, 0.25, and 0.3, or a tract turning angle >60 degrees were encountered. In 9 patients we were able to reconstruct brain fiber tracts at biopsy loci (2-32% tumor infiltration) using an FA threshold of 0.15 and 0.2, but not for a threshold of 0.25 or 0.3. The neurological outcome demonstrated potential tumor cell infiltration of functionally intact brain fiber tracts in the range of 2-8%. These findings may be useful in planning therapeutic approaches to gliomas in the vicinity of eloquent brain regions.

In vivo quantification of intracerebral GABA by single-voxel 1H-MRS—How reproducible are the results?

Gamma aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the human brain. It plays a decisive role in a variety of nervous system disorders, such as anxiety disorders, epilepsy, schizophrenia, insomnia, and many others. The reproducibility of GABA quantification results obtained with a single-voxel spectroscopy J-difference editing sequence with Point Resolved Spectroscopy localization (MEGA-PRESS) was determined on a 3.0 Tesla MR scanner in healthy adults. Eleven volunteers were measured in long- and short-term intervals. Intra- and inter-subject reproducibility were evaluated. Internal referencing of GABA+ to total creatine (tCr) and water (H(2)O), as well as two different post-processing methods for the evaluation (signal integration and time-domain fitting) were compared. In all subjects lower coefficient of variation and therefore higher reproducibility can be observed for fitting compared to integration. The GABA+/tCr ratio performs better than the GABA+/H(2)O ratio or GABA+ without internal referencing for both fitting and integration (GABA+/tCr: 13.3% and 17.0%; GABA+/H(2)O: 15.0% and 17.8%; GABA+: 19.2% and 21.7%). Four-day measurements on three subjects showed higher intra- than inter-subject reproducibility (GABA+/tCr approximately 10-12%). With a coefficient of variation of about 13% for inter-subject and 10-12% for intra-subject variability of GABA+/tCr, this technique seems to be a precise tool that can detect GABA confidently. The results of this study show the reproducibility limitations of GABA quantification in vivo, which are necessary for further clinical studies.

Proton Magnetic Resonance Spectroscopic Imaging Integrated into Image-guided Surgery: Correlation to Standard Magnetic Resonance Imaging and Tumor Cell Density

OBJECTIVE: In this study, we attempted to improve the delineation of the infiltration zone in gliomas using proton magnetic resonance spectroscopic imaging (1H MRSI). In conventional magnetic resonance imaging (MRI), the boundaries of gliomas sometimes are underestimated. 1H MRSI is a noninvasive tool that can be used to investigate the spatial distribution of metabolic changes in brain lesions. The purpose was to correlate tumor cell density from histopathological specimens with metabolic levels and the coregistered metabolic maps. METHODS: We developed a method to integrate spectroscopic data depicted as metabolic maps of biochemically pathological tissue into frameless stereotaxy. In seven patients harboring gliomas, we performed 1H MRSI with high spatial resolution and evaluated the spectral data. An algorithm was developed for user-independent calculation of pathological voxels and for visualization as metabolic maps. These maps were integrated into a three-dimensional MRI data set used for frameless stereotaxy. Stereotactic biopsies were taken from three different areas in and around the tumor involving the maximum pathological change, the border zone, and an area from outside the spectroscopically suspicious area. These specimens were correlated to the exact voxel positions in the stereotactic image space and evaluated histopathologically. RESULTS: In all cases, the implementation of the metabolic maps into frameless stereotaxy was successful, and stereotactic biopsies were acquired by use of the spectral data. A relation could be demonstrated between the metabolic changes and tumor cell density ranging from 60 to 100% in the maximum pathological area to 5 to 15% in the border zone. Interestingly, the tumor areas defined by the metabolic maps and histopathologically confirmed by biopsy exceeded the T2-weighted signal change in all cases, ranging from 6 to 32% in the examined volume. CONCLUSION: Our preliminary data suggest that 1H MRSI may be useful in combination with frameless stereotaxy to define more exactly the tumor infiltration zone in glioma surgery compared with conventional anatomic MRI alone.

Age-related degradation in the central nervous system: assessment with diffusion-tensor imaging and quantitative fiber tracking.

PURPOSE To prospectively quantify differences in age-related changes in the diffusivity parameters and fiber characteristics between association, callosal, and projection fibers. MATERIALS AND METHODS This study was approved by the institutional review board, and informed consent was obtained. Diffusion-tensor imaging data with an isotropic voxel size of 1.9 mm(3) were acquired at 3 T in 38 healthy volunteers (age range, 18-88 years; 18 women). Quantitative fiber tracking was used to calculate fractional anisotropy (FA) and mean diffusivity values, eigenvalues (lambda(1), lambda(2), and lambda(3)), the number of fiber projections, and the number of fiber projections per voxel for three-dimensional reconstructed association, callosal, projection, and total brain fibers. Bivariate linear regression models were used to analyze correlations. Significant differences between correlations were assessed with the Hotelling-Williams test. RESULTS For FA, the strongest degradation in association fibers and no significant changes in projection fibers were observed. The difference in correlation was significant (P = .002). The number of fiber projections and the number of fiber projections per voxel showed strong to moderate negative correlations that were dependent on age (P < .001) in the three fiber structures and total brain fibers, with the exception of the number of fiber projections per voxel in projection fibers, which showed no significant correlation. The decrease in the number of fiber projections was significantly greater (P = .043) in projection fibers than in total brain fibers, whereas the decrease in the number of fiber projections per voxel was significantly weaker (P = .005). Association fibers showed the largest changes per decade of age for FA (-1.13%) and for the number of fiber projections per voxel (-4.7%), whereas callosal fibers showed the largest changes per decade of age for the number of fiber projections (-10.4%). CONCLUSION Quantitative fiber tracking enables identification of differences in diffusivity and fiber characteristics due to normal aging.

Molecular imaging of cancer: MR spectroscopy and beyond.

Proton magnetic resonance spectroscopic imaging is a non-invasive diagnostic tool for the investigation of cancer metabolism. As an adjunct to morphologic and dynamic magnetic resonance imaging, it is routinely used for the staging, assessment of treatment response, and therapy monitoring in brain, breast, and prostate cancer. Recently, its application was extended to other cancerous diseases, such as malignant soft-tissue tumours, gastrointestinal and gynecological cancers, as well as nodal metastasis. In this review, we discuss the current and evolving clinical applications of proton magnetic resonance spectroscopic imaging. In addition, we will briefly discuss other evolving techniques, such as phosphorus magnetic resonance spectroscopic imaging, sodium imaging and diffusion-weighted imaging in cancer assessment.

Metabolic Imaging of Cerebral Gliomas: Spatial Correlation of Changes in O-(2-18F-Fluoroethyl)-l-Tyrosine PET and Proton Magnetic Resonance Spectroscopic Imaging

The aim of this study was to determine the spatial correlation of O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) uptake and the concentrations of choline (Cho), creatine (Cr), and total N-acetylaspartate (tNAA) determined with proton magnetic resonance spectroscopic imaging (1H MRSI) in cerebral gliomas for the multimodal evaluation of metabolic changes. Methods: 18F-FET PET and 2-dimensional 1H MRSI were performed in 15 patients with cerebral gliomas of World Health Organization (WHO) grades II–IV. PET and 1H MRSI datasets were coregistered by use of mutual information. On the basis of their levels of 18F-FET uptake, 4 different areas in a tumor (maximum, strong, moderate, and low 18F-FET uptake) were defined on PET slices as being congruent with the volume of interest in the 1H MRSI experiment. 18F-FET uptake in lesions was evaluated as tumor-to-brain ratios. Metabolite concentrations for Cho, Cr, and tNAA and Cho/tNAA ratios were computed for these 4 areas in the tumor and for the contralateral normal brain. Results: In the area with maximum 18F-FET uptake, the concentration of tNAA (R = −0.588) and the Cho/tNAA ratio (R = 0.945) correlated significantly with 18F-FET uptake. In the areas with strong and moderate 18F-FET uptake, only the Cho/tNAA ratios (R = 0.811 and R = 0.531, respectively) were significantly associated with amino acid transport. At low 18F-FET uptake, analysis of the correlations of amino acid uptake and metabolite concentrations yielded a significant result only for the concentration of Cr (R = 0.626). No correlation was found for metabolite concentrations determined with 1H MRSI and 18F-FET uptake in normal brain tissue. Maximum 18F-FET uptake and the tNAA concentration were significantly different between gliomas of WHO grades II and IV, with P values of 0.032 and 0.016, respectively. Conclusion: High 18F-FET uptake, which is indicative of tumor cell infiltration, associates with neuronal cell loss (tNAA) and changes in ratios between parameters representing membrane proliferation and those of neuronal loss (Cho/tNAA ratio), which can be measured by 1H MRSI. The significant correlation coefficients detected for Cr in regions with low 18F-FET uptake suggests an association between the mechanism governing amino acid transport and energy metabolism in areas that are infiltrated by tumor cells to a lesser extent. These findings motivate further research directed at investigating the potential of 1H MRSI to define tumor boundaries in a manner analogous to that of amino acid PET.

Accelerated time-resolved three-dimensional MR velocity mapping of blood flow patterns in the aorta using SENSE and k-t BLAST.

PURPOSE To assess the feasibility and potential limitations of the acceleration techniques SENSE and k-t BLAST for time-resolved three-dimensional (3D) velocity mapping of aortic blood flow. Furthermore, to quantify differences in peak velocity versus heart phase curves. MATERIALS AND METHODS Time-resolved 3D blood flow patterns were investigated in eleven volunteers and two patients suffering from aortic diseases with accelerated PC-MR sequences either in combination with SENSE (R=2) or k-t BLAST (6-fold). Both sequences showed similar data acquisition times and hence acceleration efficiency. Flow-field streamlines were calculated and visualized using the GTFlow software tool in order to reconstruct 3D aortic blood flow patterns. Differences between the peak velocities from single-slice PC-MRI experiments using SENSE 2 and k-t BLAST 6 were calculated for the whole cardiac cycle and averaged for all volunteers. RESULTS Reconstruction of 3D flow patterns in volunteers revealed attenuations in blood flow dynamics for k-t BLAST 6 compared to SENSE 2 in terms of 3D streamlines showing fewer and less distinct vortices and reduction in peak velocity, which is caused by temporal blurring. Solely by time-resolved 3D MR velocity mapping in combination with SENSE detected pathologic blood flow patterns in patients with aortic diseases. For volunteers, we found a broadening and flattering of the peak velocity versus heart phase diagram between the two acceleration techniques, which is an evidence for the temporal blurring of the k-t BLAST approach. CONCLUSION We demonstrated the feasibility of SENSE and detected potential limitations of k-t BLAST when used for time-resolved 3D velocity mapping. The effects of higher k-t BLAST acceleration factors have to be considered for application in 3D velocity mapping.