Carolin Reischauer

Bone metastases from prostate cancer: assessing treatment response by using diffusion-weighted imaging and functional diffusion maps--initial observations.

PURPOSE To prospectively investigate and monitor the response to antiandrogen treatment of bone metastases in patients with prostate cancer by using diffusion-weighted (DW) magnetic resonance (MR) imaging with the apparent diffusion coefficient (ADC) and functional diffusion maps (DMs). MATERIALS AND METHODS This study had institutional review board approval; informed consent was obtained from all patients. Nine treatment-naive men (mean age, 73 years; range, 66-86 years) with 20 pelvic bone metastases were included. Imaging was performed before antiandrogen treatment and at 1, 2, and 3 months afterward. Imaging included a DW MR imaging sequence with five b factors (0-800 sec/mm²). Serum prostate-specific antigen (PSA) levels and mean ADCs of each metastasis were measured over time and analyzed by using the general linear model. Pairwise comparisons (paired-samples t tests) of PSA levels and ADCs before and after therapy were performed with the significance level set at P < .017 (Bonferroni correction). To determine the relationship between serum PSA level and the averaged mean ADCs in each patient, the two parameters were correlated across time. In addition, an analysis with functional DMs was performed to evaluate ADC response to treatment on a per-voxel basis. RESULTS Serum PSA levels decreased by more than 90% during therapy. The mean ADCs of metastases were increased significantly at 1 (P < .001), 2 (P = .002), and 3 (P = .011) months after therapy compared with pretreatment values. Heterogeneous response was revealed at functional DM analysis. After 1 month of therapy, 47.3% of all analyzed tumor voxels showed significantly increased ADCs, while 46.5% were unchanged and 6.2% exhibited decreased ADCs in comparison to the pretreatment values. At 3 months after therapy, the proportion of voxels showing ADC decrease was higher (13.7%) than that at 1 month. CONCLUSION DW MR imaging allows monitoring of antiandrogen therapy in bone metastases. PSA level decrease corresponded well with an increase in mean tumor ADC. Heterogeneity of tumor response to therapy was demonstrated by functional DM analysis.

Combining fMRI and DTI: a framework for exploring the limits of fMRI-guided DTI fiber tracking and for verifying DTI-based fiber tractography results.

A powerful, non-invasive technique for estimating and visualizing white matter tracts in the human brain in vivo is white matter fiber tractography that uses magnetic resonance diffusion tensor imaging. The success of this method depends strongly on the capability of the applied tracking algorithm and the quality of the underlying data set. However, DTI-based fiber tractography still lacks standardized validation. In the present work, a combined fMRI/DTI study was performed, both to develop a setup for verifying fiber tracking results using fMRI-derived functional connections and to explore the limitations of fMRI based DTI fiber tracking. Therefore, a minor fiber bundle that features several fiber crossings and intersections was examined: The striatum and its connections to the primary motor cortex were examined by using two approaches to derive the somatotopic organization of the striatum. First, an fMRI-based somatotopic map of the striatum was reconstructed, based on fMRI activations that were provoked by unilateral motor tasks. Second, fMRI-guided DTI fiber tracking was performed to generate DTI-based somatotopic maps, using a standard line propagation and an advanced fast marching algorithm. The results show that the fiber connections reconstructed by the advanced fast marching algorithm are in good agreement with known anatomy, and that the DTI-revealed somatotopy is similar to the fMRI somatotopy. Furthermore, the study illustrates that the combination of fMRI with DTI can supply additional information in order to choose reasonable seed regions for generating functionally relevant networks and to validate reconstructed fibers.

Reconstruction of the human visual system based on DTI fiber tracking.

To apply and to evaluate the newly developed advanced fast marching algorithm (aFM) in vivo by reconstructing the human visual pathway, which is characterized by areas of extensive fiber crossing and branching, i.e., the optic chiasm and the lateral geniculate nucleus (LGN).

High-resolution diffusion tensor imaging of prostate cancer using a reduced FOV technique.

OBJECTIVE Diffusion tensor imaging (DTI) offers the promise of improved tumor localization in prostate cancer but the technique suffers from susceptibility-induced artifacts that limit the achievable resolution. The present work employs a reduced field-of-view technique that enables high-resolution DTI of the prostate at 3T. Feasibility of the approach is demonstrated in a clinical study including 26 patients and 14 controls. MATERIALS AND METHODS Reduced field-of-view acquisition was established by non-coplanar application of the excitation and the refocusing pulse in conjunction with outer volume suppression. Accuracy for cancer detection of apparent diffusion coefficient (ADC) mapping and T2-weighted imaging was calculated and compared with reference to the findings of trans-rectal ultrasound-guided octant biopsy. Mean ADCs and fractional anisotropy (FA) values in the patients with positive and negative biopsies were compared to each other and to the controls. RESULTS Fine anatomical details were successfully depicted on the ADC maps with sub-millimeter resolution. Accuracy for prostate cancer detection was 73.5% for ADC maps and 71% for T2-weighted images, respectively. Cohens kappa (κ=0.48) indicated moderate agreement of the two methods. The mean ADCs were significantly lower, the FA values higher, in the patients with positive biopsy than in the patients with negative biopsy and the controls. Monte Carlo simulations showed that the FA values, but not the ADCs, were slightly overestimated. Bootstrap analysis revealed that the ADC, but not the FA value, is a highly repeatable marker. CONCLUSION In conclusion, the present work introduces a new approach for high-resolution DTI of the prostate enabling a more accurate detection of focal tumors especially useful in screening populations or as a potential navigator for image-guided biopsy.

Construction of a temperature-controlled diffusion phantom for quality control of diffusion measurements

To construct a temperature‐controlled diffusion phantom with known diffusion properties and geometry in order to facilitate the comparison and optimization of diffusion sequences with the objective of increasing the precision of experimentally derived diffusion parameters.

Three-dimensional alignment of the aggregated myocytes in the normal and hypertrophic murine heart

Several observations suggest that the transmission of myocardial forces is influenced in part by the spatial arrangement of the myocytes aggregated together within ventricular mass. Our aim was to assess, using diffusion tensor magnetic resonance imaging (DT-MRI), any differences in the three-dimensional arrangement of these myocytes in the normal heart compared with the hypertrophic murine myocardium. We induced ventricular hypertrophy in seven mice by infusion of angiotensin II through a subcutaneous pump, with seven other mice serving as controls. DT-MRI of explanted hearts was performed at 3.0 Tesla. We used the primary eigenvector in each voxel to determine the three-dimensional orientation of aggregated myocytes in respect to their helical angles and their transmural courses (intruding angles). Compared with controls, the hypertrophic hearts showed significant increases in myocardial mass and the outer radius of the left ventricular chamber (P < 0.05). In both groups, a significant change was noted from positive intruding angles at the base to negative angles at the ventricular apex (P < 0.01). Compared with controls, the hypertrophied hearts had significantly larger intruding angles of the aggregated myocytes, notably in the apical and basal slices (P < 0.001). In both groups, the helical angles were greatest in midventricular sections, albeit with significantly smaller angles in the mice with hypertrophied myocardium (P < 0.01). The use of DT-MRI revealed significant differences in helix and intruding angles of the myocytes in the mice with hypertrophied myocardium.

Early Treatment Response in Non-Small Cell Lung Cancer Patients Using Diffusion-Weighted Imaging and Functional Diffusion Maps - A Feasibility Study

Objective The aim of this study was to prospectively evaluate the feasibility of monitoring treatment response to chemotherapy in patients with non-small cell lung carcinoma using functional diffusion maps (fDMs). Materials and Methods This study was approved by the Cantonal Research Ethics Committee and informed written consent was obtained from all patients. Nine patients (mean age = 66 years; range = 53–76 years, 5 females, 4 males) with overall 13 lesions were included. Imaging was performed within two weeks before initiation of chemotherapy and at one, two, and six weeks after initiation of chemotherapy. Imaging included a respiratory-triggered diffusion-weighted sequence including three b-factors (100, 600, and 800 s/mm2). Treatment response was defined by change in tumor diameter on computed tomography (CT) after two cycles of chemotherapy. Changes in the apparent diffusion coefficient (ADC) on a per-lesion basis and the percentages of voxel with significantly increased or decreased ADCs on fDMs were analyzed using repeated measures analysis of variance (ANOVA). Changes in tumor size were used as covariate to examine the ability of ADCs and fDM parameters to predict treatment response. Results Repeated measures ANOVA revealed that the percentage of voxels with increased ADCs on fDMs (p = 0.002) as well as the mean ADC increase (p = 0.011) were significantly higher in good responders with a large reduction in tumor size on CT. Conclusion Our results indicate that the percentage of voxels with significantly increased ADCs on fDMs seems to be a promising biomarker for early prediction of treatment response in patients with non-small cell lung carcinoma. Contrary to averaged values, this approach allows the spatial heterogeneity of treatment response to be resolved.

BootGraph: probabilistic fiber tractography using bootstrap algorithms and graph theory.

Bootstrap methods have recently been introduced to diffusion-weighted magnetic resonance imaging to estimate the measurement uncertainty of ensuing diffusion parameters directly from the acquired data without the necessity to assume a noise model. These methods have been previously combined with deterministic streamline tractography algorithms to allow for the assessment of connection probabilities in the human brain. Thereby, the local noise induced disturbance in the diffusion data is accumulated additively due to the incremental progression of streamline tractography algorithms. Graph based approaches have been proposed to overcome this drawback of streamline techniques. For this reason, the bootstrap method is in the present work incorporated into a graph setup to derive a new probabilistic fiber tractography method, called BootGraph. The acquired data set is thereby converted into a weighted, undirected graph by defining a vertex in each voxel and edges between adjacent vertices. By means of the cone of uncertainty, which is derived using the wild bootstrap, a weight is thereafter assigned to each edge. Two path finding algorithms are subsequently applied to derive connection probabilities. While the first algorithm is based on the shortest path approach, the second algorithm takes all existing paths between two vertices into consideration. Tracking results are compared to an established algorithm based on the bootstrap method in combination with streamline fiber tractography and to another graph based algorithm. The BootGraph shows a very good performance in crossing situations with respect to false negatives and permits incorporating additional constraints, such as a curvature threshold. By inheriting the advantages of the bootstrap method and graph theory, the BootGraph method provides a computationally efficient and flexible probabilistic tractography setup to compute connection probability maps and virtual fiber pathways without the drawbacks of streamline tractography algorithms or the assumption of a noise distribution. Moreover, the BootGraph can be applied to common DTI data sets without further modifications and shows a high repeatability. Thus, it is very well suited for longitudinal studies and meta-studies based on DTI.

Insula-Specific 1H Magnetic Resonance Spectroscopy Reactions in Heavy Smokers under Acute Nicotine Withdrawal and after Oral Nicotine Substitution

The aim of this study was to clarify whether addiction-specific neurometabolic reaction patterns occur in the insular cortex during acute nicotine withdrawal in tobacco smokers in comparison to nonsmokers. Fourteen male smokers and 10 male nonsmokers were included. Neurometabolites of the right and the left insular cortices were quantified by magnetic resonance spectroscopy (MRS) on a 3-Tesla scanner. Three separate MRS measurements were performed in each subject: among the smokers, the first measurement was done during normal smoking behavior, the second measurement during acute withdrawal (after 24 h of smoking abstinence), and the third shortly after administration of an oral nicotine substitute. Simultaneously, craving, withdrawal symptoms, and CO levels in exhaled air were determined during the three phases. The participants in the control group underwent the same MR protocol. In the smokers, during withdrawal, the insular cortex showed a significant increase in glutamine (Gln; p = 0.023) as well as a slight increase not reaching significance for glutamine/glutamate (Glx; p = 0.085) and a nonsignificant drop in myoinositol (mI; p = 0.381). These values tended to normalize after oral nicotine substitution treatment, even though differences were not significant: Gln (p = 0.225), Glx (p = 0.107) and mI (p = 0.810). Overall, the nonsmokers (control group) did not show any metabolic changes over all three phases (p > 0.05). In smokers, acute nicotine withdrawal produces a neurometabolic reaction pattern that is partly reversed by the administration of an oral nicotine substitute. The results are consistent with the expression of an addiction-specific neurometabolic shift in the brain and confirm the fact that the insular cortex seems to play a possible role in nicotine dependence.

Optimizing signal‐to‐noise ratio of high‐resolution parallel single‐shot diffusion‐weighted echo‐planar imaging at ultrahigh field strengths

The potential signal‐to‐noise ratio (SNR) gain at ultrahigh field strengths offers the promise of higher image resolution in single‐shot diffusion‐weighted echo‐planar imaging the challenge being reduced T2 and T2* relaxation times and increased B0 inhomogeneity which lead to geometric distortions and image blurring. These can be addressed using parallel imaging (PI) methods for which a greater range of feasible reduction factors has been predicted at ultrahigh field strengths—the tradeoff being an associated SNR loss. Using comprehensive simulations, the SNR of high‐resolution diffusion‐weighted echo‐planar imaging in combination with spin‐echo and stimulated‐echo acquisition is explored at 7 T and compared to 3 T. To this end, PI performance is simulated for coil arrays with a variable number of circular coil elements. Beyond that, simulations of the point spread function are performed to investigate the actual image resolution. When higher PI reduction factors are applied at 7 T to address increased image distortions, high‐resolution imaging benefits SNR‐wise only at relatively low PI reduction factors. On the contrary, it features generally higher image resolutions than at 3 T due to smaller point spread functions. The SNR simulations are confirmed by phantom experiments. Finally, high‐resolution in vivo images of a healthy volunteer are presented which demonstrate the feasibility of higher PI reduction factors at 7 T in practice. Magn Reson Med, 2012.