Wolfgang Bogner

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.

Assessment of 31P relaxation times in the human calf muscle: A comparison between 3 T and 7 T in vivo

Phosphorus (31P) T1 and T2 relaxation times in the resting human calf muscle were assessed by interleaved, surface coil localized inversion recovery and frequency‐selective spin‐echo at 3 and 7 T. The obtained T1 (mean ± SD) decreased significantly (P < 0.05) from 3 to 7 T for phosphomonoesters (PME) (8.1 ± 1.7 s to 3.1 ± 0.9 s), phosphodiesters (PDE) (8.6 ± 1.2 s to 6.0 ± 1.1 s), phosphocreatine (PCr) (6.7 ± 0.4 s to 4.0 ± 0.2 s), γ‐NTP (nucleotide triphosphate) (5.5 ± 0.4 s to 3.3 ± 0.2 s), α‐NTP (3.4 ± 0.3 s to 1.8 ± 0.1 s), and β‐NTP (3.9 ± 0.4 s to 1.8 ± 0.1 s), but not for inorganic phosphate (Pi) (6.9 ± 0.6 s to 6.3 ± 1.0 s). The decrease in T2 was significant for Pi (153 ± 9 ms to 109 ± 17 ms), PDE (414 ± 128 ms to 314 ± 35 ms), PCr (354 ± 16 ms to 217 ± 14 ms), and γ‐NTP (61.9 ± 8.6 ms to 29.0 ± 3.3 ms). This decrease in T1 with increasing field strength of up to 62% can be explained by the increasing influence of chemical shift anisotropy on relaxation mechanisms and may allow shorter measurements at higher field strengths or up to 62% additional signal‐to‐noise ratio (SNR) per unit time. The fully relaxed SNR increased by +96%, while the linewidth increased from 6.5 ± 1.2 Hz to 11.2 ± 1.9 Hz or +72%. At 7 T 31P‐MRS in the human calf muscle offers more than twice as much SNR per unit time in reduced measurement time compared to 3 T. This will facilitate in vivo 31P‐MRS of the human muscle at 7 T. Magn Reson Med, 2009.

A combined high temporal and high spatial resolution 3 Tesla MR imaging protocol for the assessment of breast lesions: initial results.

Purpose:To develop a 3.0 Tesla breast imaging protocol that combines high temporal and spatial resolution three-dimensional MR sequences for quantitative time course and morphologic analysis of breast lesions. Materials and Methods:Thirty-four patients were included in the study (age range, 31–82; mean age, 54.3). The study protocol was approved by the Institutional Review Board and written informed consent was obtained from all patients. The magnetic resonance imaging protocol included: a coronal T1-weighted volume-interpolated-breathhold-examination sequence, focused on high temporal resolution for optimal assessment of the contrast-enhancement behavior of lesions (SI 1.7 mm isotropic; TA 3.45 minutes for 17 measurements); a coronal T1-weighted turbo fast-low-angle-shot-three-dimensional sequence, with water-excitation and fat suppression, focused on high spatial resolution for morphologic analysis (SI 1 mm isotropic; TA 2 minutes); and a repeated coronal volume-interpolated-breathhold-examination sequence for detection of washout. Lesion size and morphology were assessed. Region-of-interests for suspicious areas were manually drawn and evaluated for contrast-enhancement behavior by plotting intensity courses against time. Sensitivity and specificity with a 95% confidence interval and the negative predictive value and positive predictive value were calculated. Diagnostic accuracy was assessed. The histopathological diagnoses were used as a standard of reference. Results:Fifty-five lesions were detected in 34 patients. All malignant breast lesions were identified correctly. There were 5 false-positive lesions. The sensitivity of contrast-enhanced magnetic resonance imaging of the breast at 3 T was 100%, with a 95% confidence interval (CI) of 90.6% to 100%. The specificity was 72.2%, with a 95% CI of 49.1% to 87.5%. The positive predictive value was 0.88 and the negative predictive value was 1. Diagnostic accuracy was 91% with a 95% CI of 80.4% to 96.1%. Conclusion:Our prospective study demonstrates that the presented 3 Tesla MR imaging protocol, comprising both high temporal and high spatial resolution, enables accurate detection and assessment of breast lesions.

Readout-segmented Echo-planar Imaging Improves the Diagnostic Performance of Diffusion-weighted MR Breast Examinations at 3.0 T

PURPOSE To qualitatively and quantitatively compare the diagnostic value of diffusion-weighted (DW) magnetic resonance (MR) imaging based on standard single-shot echo-planar imaging and readout-segmented echo-planar imaging in patients with breast cancer at 3.0 T. MATERIALS AND METHODS Institutional review board approval and written informed consent were obtained. Forty-seven patients with 49 histopathologically verified lesions were included in this study. In all patients, DW imaging, with single-shot echo-planar imaging and readout-segmented echo-planar imaging with comparable imaging parameters, was performed with a 3.0-T MR imager. Two independent readers visually assessed image quality and lesion conspicuity, and image properties (ie, signal-to-noise ratio, contrast, geometric distortions) were quantified. Regions of interest were drawn in all lesions (28 malignant, 21 benign) and in the normal breast parenchyma to investigate differences in apparent diffusion coefficient (ADC). Diagnostic accuracy was calculated on the basis of an ADC threshold of 1.25 × 10(-3) mm(2)/sec. RESULTS Each reader found a higher diagnostic accuracy for readout-segmented (96%) than for single-shot (90%) echo-planar imaging. The area under the curve for readout-segmented echo-planar imaging (0.981) was significantly larger than for single-shot echo-planar imaging (0.867) (P = .026). There was no significant difference in the ADC obtained by using either DW imaging method. Lesion conspicuity and image quality of readout-segmented echo-planar imaging were rated superior to those of single-shot echo-planar imaging (P < .001). Readout-segmented echo-planar imaging reduced geometric distortions by a factor of three. CONCLUSION DW imaging based on readout-segmented echo-planar imaging provided significantly higher image quality and lesion conspicuity than single-shot echo-planar imaging by reducing geometric distortions, image blurring, and artifact level with a clinical high-field-strength MR imager. Thereby, readout-segmented echo-planar imaging reached a higher diagnostic accuracy for the differentiation of benign and malignant breast lesions.

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.

Improved diagnostic accuracy with multiparametric magnetic resonance imaging of the breast using dynamic contrast-enhanced magnetic resonance imaging, diffusion-weighted imaging, and 3-dimensional proton magnetic resonance spectroscopic imaging.

IntroductionThe purpose of this study was to compare the diagnostic accuracy of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) as a single parameter to multiparametric (MP) MRI with 2 (DCE MRI and diffusion-weighted imaging [DWI]) and 3 (DCE MRI, DWI, and 3-dimensional proton magnetic resonance spectroscopic imaging [3D 1H-MRSI]) parameters in breast cancer diagnosis. Materials and MethodsThis prospective study was approved by the institutional review board. Written informed consent was obtained in all patients. One hundred thirteen female patients (mean age, 52 years; range, 22–86 years) with an imaging abnormality (Breast Imaging Reporting and Data System 0, 4–5) were included in this study. Multiparametric MRI of the breast at 3 T with DCE MRI, DWI, and 3D 1H-MRSI was performed. The likelihood of malignancy was assessed for DCE MRI and MP MRI with 2 (DCE MRI and DWI) and 3 (DCE MRI, DWI, and 3D 1H-MRSI) parameters separately. Histopathology was used as the standard of reference. Appropriate statistical tests were used to assess sensitivity, specificity, and diagnostic accuracy for each assessment combination. ResultsThere were 74 malignant and 39 benign breast lesions. Multiparametric MRI with 3 MRI parameters yielded significantly higher areas under the curve (0.936) in comparison with DCE MRI alone (0.814) (P < 0.001). Multiparametric MRI with just 2 parameters at 3 T did not yield higher areas under the curve (0.808) than did DCE MRI alone (0.814). Multiparametric MRI with 3 parameters resulted in elimination of false-negative lesions and significantly reduced the false-positives ones (P = 0.002). ConclusionsMultiparametric MRI with 3 parameters increases the diagnostic accuracy of breast cancer in comparison with DCE-MRI alone and MP MRI with 2 parameters.

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.

Three-dimensional Proton MR Spectroscopic Imaging at 3 T for the Differentiation of Benign and Malignant Breast Lesions

PURPOSE To evaluate the diagnostic accuracy of quantitative, three-dimensional (3D) magnetic resonance (MR) spectroscopic imaging at 3 T for the differentiation of benign and malignant breast lesions, on the basis of choline (Cho) signal-to-noise ratio (SNR) threshold levels, in a clinically feasible measurement time. MATERIALS AND METHODS Institutional review board approval and written informed consent were obtained from all subjects. Fifty female patients (mean age, 50 years; age range, 25-82 years) with mammographic or ultrasonographic (US) abnormalities were successfully examined in the prone position with a 3-T MR system by using a dedicated breast coil. Lesions were verified by either histopathologic examination or follow-up of at least 24 months. For 3D MR spectroscopic imaging, a point-resolved spectroscopic sequence (repetition time msec/echo time msec, 750/145; field of view, 12 × 12 × 12 cm(3); matrix size, 12 × 12 × 12, interpolated to 16 × 16 × 16; acquisition time, 11 minutes 17 seconds) was used. The maximum Cho SNR was assessed in all lesions and correlated with the histopathologic results. RESULTS Thirty-two malignant and 12 benign lesions were confirmed in 43 patients with histopathologic examination. Seven patients without biopsy underwent imaging follow-up. In 31 of 32 (97%) malignant and 10 of 19 (53%) benign lesions, Cho was detected. The median Cho SNR in malignant lesions was 5.7, compared with 2.0 in benign lesions. With a Cho SNR threshold level of 2.6, 3D MR spectroscopic imaging provided a sensitivity of 97% and a specificity of 84% for the differentiation of benign and malignant breast lesions. CONCLUSION At 3T, 3D MR spectroscopic imaging yields high diagnostic sensitivity and specificity for discrimination of benign and malignant breast lesions within reasonable measurement times. This technique allows the study of heterogeneous and multicentric breast tumors and simplifies acquisition planning.

Treatment Response Assessment in IDH-Mutant Glioma Patients by Noninvasive 3D Functional Spectroscopic Mapping of 2-Hydroxyglutarate.

Purpose: Measurements of objective response rates are critical to evaluate new glioma therapies. The hallmark metabolic alteration in gliomas with mutant isocitrate dehydrogenase (IDH) is the overproduction of oncometabolite 2-hydroxyglutarate (2HG), which plays a key role in malignant transformation. 2HG represents an ideal biomarker to probe treatment response in IDH-mutant glioma patients, and we hypothesized a decrease in 2HG levels would be measureable by in vivo magnetic resonance spectroscopy (MRS) as a result of antitumor therapy. Experimental Design: We report a prospective longitudinal imaging study performed in 25 IDH-mutant glioma patients receiving adjuvant radiation and chemotherapy. A newly developed 3D MRS imaging was used to noninvasively image 2HG. Paired Student t test was used to compare pre- and posttreatment tumor 2HG values. Test–retest measurements were performed to determine the threshold for 2HG functional spectroscopic maps (fSM). Univariate and multivariate regression were performed to correlate 2HG changes with Karnofsky performance score (KPS). Results: We found that mean 2HG (2HG/Cre) levels decreased significantly (median = 48.1%; 95% confidence interval = 27.3%–56.5%; P = 0.007) in the posttreatment scan. The volume of decreased 2HG correlates (R2 = 0.88, P = 0.002) with clinical status evaluated by KPS. Conclusions: We demonstrate that dynamic measurements of 2HG are feasible by 3D fSM, and the decrease of 2HG levels can monitor treatment response in patients with IDH-mutant gliomas. Our results indicate that quantitative in vivo 2HG imaging may be used for precision medicine and early response assessment in clinical trials of therapies targeting IDH-mutant gliomas. Clin Cancer Res; 22(7); 1632–41. ©2015 AACR.

High‐resolution mapping of human brain metabolites by free induction decay 1H MRSI at 7 T

This work describes a new approach for high‐spatial‐resolution 1H MRSI of the human brain at 7 T. 1H MRSI at 7 T using conventional approaches, such as point‐resolved spectroscopy and stimulated echo acquisition mode with volume head coils, is limited by technical difficulties, including chemical shift displacement errors, B0/B1 inhomogeneities, a high specific absorption rate and decreased T2 relaxation times. The method presented here is based on free induction decay acquisition with an ultrashort acquisition delay (TE*) of 1.3 ms. This allows full signal detection with negligible T2 decay or J‐modulation. Chemical shift displacement errors were reduced to below 5% per part per million in the in‐slice direction and were eliminated in‐plane. The B1 sensitivity was reduced significantly and further corrected using flip angle maps. Specific absorption rate requirements were well below the limit (~20 % = 0.7 W/kg). The suppression of subcutaneous lipid signals was achieved by substantially improving the point‐spread function. High‐quality metabolic mapping of five important brain metabolites was achieved with high in‐plane resolution (64 × 64 matrix with a 3.4 × 3.4 × 12 mm3 nominal voxel size) in four healthy subjects. The ultrashort TE* increased the signal‐to‐noise ratio of J‐coupled resonances, such as glutamate and myo‐inositol, several‐fold to enable the mapping of even these metabolites with high resolution. Four measurement repetitions in one healthy volunteer provided proof of the good reproducibility of this method. The high spatial resolution allowed the visualization of several anatomical structures on metabolic maps. Free induction decay MRSI is insensitive to T2 decay, J‐modulation, B1 inhomogeneities and chemical shift displacement errors, and overcomes specific absorption rate restrictions at ultrahigh magnetic fields. This makes it a promising method for high‐resolution 1H MRSI at 7 T and above. Copyright