Faculty Bibliography

PURPOSE: To examine heterogeneous breast cancer through intravoxel incoherent motion (IVIM) histogram analysis. MATERIALS AND METHODS: This HIPAA-compliant, IRB-approved retrospective study included 62 patients (age 48.44 +/- 11.14 years, 50 malignant lesions and 12 benign) who underwent contrast-enhanced 3 T breast MRI and diffusion-weighted imaging. Apparent diffusion coefficient (ADC) and IVIM biomarkers of tissue diffusivity (Dt), perfusion fraction (fp), and pseudo-diffusivity (Dp) were calculated using voxel-based analysis for the whole lesion volume. Histogram analysis was performed to quantify tumour heterogeneity. Comparisons were made using Mann-Whitney tests between benign/malignant status, histological subtype, and molecular prognostic factor status while Spearman's rank correlation was used to characterize the association between imaging biomarkers and prognostic factor expression. RESULTS: The average values of the ADC and IVIM biomarkers, Dt and fp, showed significant differences between benign and malignant lesions. Additional significant differences were found in the histogram parameters among tumour subtypes and molecular prognostic factor status. IVIM histogram metrics, particularly fp and Dp, showed significant correlation with hormonal factor expression. CONCLUSION: Advanced diffusion imaging biomarkers show relationships with molecular prognostic factors and breast cancer malignancy. This analysis reveals novel diagnostic metrics that may explain some of the observed variability in treatment response among breast cancer patients. KEY POINTS: * Novel IVIM biomarkers characterize heterogeneous breast cancer. * Histogram analysis enables quantification of tumour heterogeneity. * IVIM biomarkers show relationships with breast cancer malignancy and molecular prognostic factors.

PURPOSE: To compare fitting methods and sampling strategies, including the implementation of an optimized b-value selection for improved estimation of intravoxel incoherent motion (IVIM) parameters in breast cancer. METHODS: Fourteen patients (age, 48.4 +/- 14.27 years) with cancerous lesions underwent 3 Tesla breast MRI examination for a HIPAA-compliant, institutional review board approved diffusion MR study. IVIM biomarkers were calculated using "free" versus "segmented" fitting for conventional or optimized (repetitions of key b-values) b-value selection. Monte Carlo simulations were performed over a range of IVIM parameters to evaluate methods of analysis. Relative bias values, relative error, and coefficients of variation (CV) were obtained for assessment of methods. Statistical paired t-tests were used for comparison of experimental mean values and errors from each fitting and sampling method. RESULTS: Comparison of the different analysis/sampling methods in simulations and experiments showed that the "segmented" analysis and the optimized method have higher precision and accuracy, in general, compared with "free" fitting of conventional sampling when considering all parameters. Regarding relative bias, IVIM parameters fp and Dt differed significantly between "segmented" and "free" fitting methods. CONCLUSION: IVIM analysis may improve using optimized selection and "segmented" analysis, potentially enabling better differentiation of breast cancer subtypes and monitoring of treatment. Magn Reson Med, 2014. (c) 2014 Wiley Periodicals, Inc.

OBJECTIVE: To measure background parenchymal enhancement (BPE) and compare with other contrast enhancement values and diffusion-weighted MRI parameters in healthy and cancerous breast tissue at the clinical level. MATERIALS AND METHODS: This HIPAA-compliant, IRB approved retrospective study enrolled 77 patients (38 patients with breast cancer - mean age 51.8+/-10.0 years; 39 high-risk patients for screening evaluation - mean age 46.3+/-11.7 years), who underwent contrast-enhanced 3T breast MRI. Contrast enhanced MRI and diffusion-weighted imaging were performed to quantify BPE, lesion contrast enhancement, and apparent diffusion coefficient (ADC) metrics in fibroglandular tissue (FGT) and lesions. RESULTS: BPE did not correlate with ADC values. Mean BPE for the lesion-bearing patients was higher (43.9%) compared to that of the high-risk screening patients (28.3%, p=0.004). Significant correlation (r=0.37, p<0.05) was found between BPE and lesion contrast enhancement. CONCLUSION: No significant association was observed between parenchymal or lesion enhancement with conventional apparent diffusion metrics, suggesting that proliferative processes are not co-regulated in cancerous and parenchymal tissue.

When diffusion biomarkers display transient changes, i.e. in muscle following exercise, traditional diffusion-tensor imaging (DTI) methods lack the temporal resolution to resolve the dynamics. This article presents an MRI method for dynamic diffusion-tensor acquisitions on a clinical 3T scanner. This method, the Single-Line Multiple-Echo Diffusion-Tensor Acquisition Technique (SL-MEDITATE), achieves a high temporal resolution (4 s) by rapid diffusion encoding through the acquisition of multiple echoes with unique diffusion sensitization and limiting the readout to a single line volume. The method is demonstrated in a rotating anisotropic phantom, a flow phantom with adjustable flow speed and in vivo skeletal calf muscle of healthy volunteers following a plantar flexion exercise. The rotating and flow-varying phantom experiments show that SL-MEDITATE correctly identifies the rotation of the first diffusion eigenvector and the changes in diffusion-tensor parameter magnitudes, respectively. Immediately following exercise, the in vivo mean diffusivity (MD) time courses show, before the well-known increase, an initial decrease that is not typically observed in traditional DTI. In conclusion, SL-MEDITATE can be used to capture transient changes in tissue anisotropy in a single line. Future progress might allow for dynamic DTI when combined with appropriate k-space trajectories and compressed sensing reconstruction

Radial spin-echo diffusion imaging allows motion-robust imaging of tissues with very low T2 values like articular cartilage with high spatial resolution and signal-to-noise ratio (SNR). However, in vivo measurements are challenging, due to the significantly slower data acquisition speed of spin-echo sequences and the less efficient k-space coverage of radial sampling, which raises the demand for accelerated protocols by means of undersampling. This work introduces a new reconstruction approach for undersampled diffusion-tensor imaging (DTI). A model-based reconstruction implicitly exploits redundancies in the diffusion-weighted images by reducing the number of unknowns in the optimization problem and compressed sensing is performed directly in the target quantitative domain by imposing a total variation (TV) constraint on the elements of the diffusion tensor. Experiments were performed for an anisotropic phantom and the knee and brain of healthy volunteers (three and two volunteers, respectively). Evaluation of the new approach was conducted by comparing the results with reconstructions performed with gridding, combined parallel imaging and compressed sensing and a recently proposed model-based approach. The experiments demonstrated improvements in terms of reduction of noise and streaking artifacts in the quantitative parameter maps, as well as a reduction of angular dispersion of the primary eigenvector when using the proposed method, without introducing systematic errors into the maps. This may enable an essential reduction of the acquisition time in radial spin-echo diffusion-tensor imaging without degrading parameter quantification and/or SNR

The purpose of this work was to carry out diffusion tensor imaging (DTI) at multiple diffusion times Td in skeletal muscle in normal subjects and chronic exertional compartment syndrome (CECS) patients and analyze the data with the random permeable barrier model (RPBM) for biophysical specificity. Using an institutional review board approved HIPAA-compliant protocol, seven patients with clinical suspicion of CECS and eight healthy volunteers underwent DTI of the calf muscle in a Siemens MAGNETOM Verio 3 T scanner at rest and after treadmill exertion at four different Td values. Radial diffusion values lambdarad were computed for each of seven different muscle compartments and analyzed with RPBM to produce estimates of free diffusivity D0 , fiber diameter a, and permeability kappa. Fiber diameter estimates were compared with measurements from literature autopsy reference for several compartments. Response factors (post/pre-exercise ratios) were computed and compared between normal controls and CECS patients using a mixed-model two-way analysis of variance. All subjects and muscle compartments showed nearly time-independent diffusion along and strongly time-dependent diffusion transverse to the muscle fibers. RPBM estimates of fiber diameter correlated well with corresponding autopsy reference. D0 showed significant (p < 0.05) increases with exercise for volunteers, and a increased significantly (p < 0.05) in volunteers. At the group level, response factors of all three parameters showed trends differentiating controls from CECS patients, with patients showing smaller diameter changes (p = 0.07), and larger permeability increases (p = 0.07) than controls. Time-dependent diffusion measurements combined with appropriate tissue modeling can provide enhanced microstructural specificity for in vivo tissue characterization. In CECS patients, our results suggest that high-pressure interfiber edema elevates free diffusion and restricts exercise-induced fiber dilation. Such specificity may be useful in differentiating CECS from other disorders or in predicting its response to either physical therapy or fasciotomy

PURPOSE: To evaluate the performance of diffusion tensor imaging (DTI) in the evaluation of chronic exertional compartment syndrome (CECS) as compared to T(2) -weighted (T2w) imaging. MATERIALS AND METHODS: Using an Institutional Review Board (IRB)-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant protocol, spectral adiabatic inversion recovery (SPAIR) T2w imaging and stimulated echo DTI were applied to eight healthy volunteers and 14 suspected CECS patients before and after exertion. Longitudinal and transverse diffusion eigenvalues, mean diffusivity (MD), and fractional anisotropy (FA) were measured in seven calf muscle compartments, which in patients were classified by their response on T2w: normal (<20% change), and CECS (>20% change). Mixed model analysis of variance compared subject groups and compartments in terms of response factors (post/pre-exercise ratios) of DTI parameters. RESULTS: All diffusivities significantly increased (P < 0.0001) and FA decreased (P = 0.0014) with exercise. Longitudinal diffusion responses were significantly smaller than transversal diffusion responses (P < 0.0001). Nineteen of 98 patient compartments were classified as CECS on T2w. MD increased by 3.8 +/- 3.4% (volunteer), 7.4 +/- 4.2% (normal), and 9.1 +/- 7.0% (CECS) with exercise. CONCLUSION: DTI shows promise as an ancillary imaging method in the diagnosis and understanding of the pathophysiology in CECS. Future studies may explore its utility in predicting response to treatment. J. Magn. Reson. Imaging 2013;. (c) 2013 Wiley Periodicals, Inc.

This article describes the concepts and implementation of an MRI method, the multiple-echo diffusion tensor acquisition technique (MEDITATE), which is capable of acquiring apparent diffusion tensor maps in two scans on a 3T clinical scanner. In each MEDITATE scan, a set of RF pulses generates multiple echoes, the amplitudes of which are diffusion weighted in both magnitude and direction by a pattern of diffusion gradients. As a result, two scans acquired with different diffusion weighting strengths suffice for accurate estimation of diffusion tensor imaging (DTI) parameters. The MEDITATE variation presented here expands previous MEDITATE approaches to adapt to the clinical scanner platform, such as exploiting longitudinal magnetization storage to reduce T2 weighting. Fully segmented multi-shot Cartesian encoding is used for image encoding. MEDITATE was tested on isotropic (agar gel), anisotropic diffusion phantoms (asparagus) and in vivo skeletal muscle in healthy volunteers with cardiac gating. Comparisons of accuracy were performed with standard twice-refocused spin echo (TRSE) DTI in each case and good quantitative agreement was found between diffusion eigenvalues, mean diffusivity and fractional anisotropy derived from TRSE DTI and from the MEDITATE sequence. Orientation patterns were correctly reproduced in both isotropic and anisotropic phantoms, and approximately for in vivo imaging. This illustrates that the MEDITATE method of compressed diffusion encoding is feasible on the clinical scanner platform. With future development and employment of appropriate view-sharing image encoding, this technique may be used in clinical applications requiring time-sensitive acquisition of DTI parameters such as dynamical DTI in muscle

In (19)F MRI oximetry, a method used to image tumour hypoxia, perfluorocarbons serve as oxygenation markers. The goal of this study is to evaluate the impact of perfluorocarbon distribution and concentration in (19)F MRI oximetry through a computer simulation. The simulation studies the correspondence between (19)F measured (pO(FNMR)(2)) and actual tissue oxygen tension (pO(2)) for several tissue perfluorocarbon distributions. For this, a Krogh tissue model is implemented which incorporates the presence of perfluorocarbons in blood and tissue. That is, in tissue the perfluorocarbons are distributed homogeneously according to Gaussian diffusion profiles, or the perfluorocarbons are concentrated in the capillary wall. Using these distributions, the oxygen tension in the simulation volume is calculated. The simulated mean oxygen tension is then compared with pO(FNMR)(2), the (19)F MRI-based measure of pO(2) and with pO(0)(2), pO(2) in the absence of perfluorocarbons. The agreement between pO(FNMR)(2) and actual pO(2) is influenced by vascular density and perfluorocarbon distribution. The presence of perfluorocarbons generally gives rise to a pO(2) increase in tissue. This effect is enhanced when perfluorocarbons are also present in blood. Only the homogeneous perfluorocarbon distribution in tissue with no perfluorocarbons in blood guarantees small deviations of pO(FNMR)(2) from pO(2). Hence, perfluorocarbon distribution in tissue and blood has a serious impact on the reliability of (19)F MRI-based measures of oxygen tension. In addition, the presence of perfluorocarbons influences the actual oxygen tension. This finding may be of great importance for further development of (19)F MRI oximetry.

Recently, novel radiochromic leucodye micelle hydrogel dosimeters were introduced in the literature. In these studies, gel measured electron depth dose profiles were compared with ion chamber depth dose data, from which it was concluded that leucocrystal violet-type dosimeters were independent of dose rate. Similar conclusions were drawn for leucomalachite green-type dosimeters, only after pre-irradiating the samples to a homogeneous radiation dose. However, in our extensive study of the radio-physical properties of leucocrystal violet- and leucomalachite green-type dosimeters, a significant dose rate dependence was found. For a dose rate variation between 50 and 400 cGy min(-1), a maximum difference of 75% was found in optical dose sensitivity for the leucomalachite green-type dosimeter. Furthermore, the measured optical dose sensitivity of the leucomalachite green-type dosimeter was four times lower than the value previously reported in the literature. For the leucocrystal violet-type dosimeter, a maximum difference in optical dose sensitivity of 55% was found between 50 and 400 cGy min(-1). A modified composition of the leucomalachite green-type dosimeter is proposed. This dosimeter is composed of gelatin, sodium dodecyl sulfate, chloroform, trichloroacetic acid and leucomalachite green. The optical dose sensitivity amounted to 4.375 x 10(-5) cm(-1) cGy(-1) (dose rate 400 cGy min(-1)). No energy dependence for photon energies between 6 and 18 MV was found. No temperature dependence during readout was found notwithstanding a temperature dependence during irradiation of 1.90 cGy degrees C(-1) increase on a total dose of 100 cGy. The novel gel dosimeter formulation exhibits an improved spatial stability (2.45 x 10(-7) cm(2) s(-1) (= 0.088 mm(2) h(-1))) and good water/soft tissue equivalence. Nevertheless, the novel formulation was also found to have a significant, albeit reduced, dose rate dependence, as a maximum difference of 33% was found in optical dose sensitivity when the dose rate varied between 50 and 400 cGy min(-1). By pre-irradiating the novel leucomalachite green-type dosimeter to 500 cGy, the apparent difference in dose response between 200 and 400 cGy min(-1) was eliminated, similar to earlier findings. However, a dose response difference of 38% between 50 and 200 cGy min(-1) was still measured. On the basis of these experimental results it is concluded that the leucodye micelle gel dosimeter is not yet optimal for dose verifications of high precision radiation therapy treatments. This study, however, indicates that the dose rate dependence has a potential for improvement. Future research is necessary to further minimize the dose rate dependence through extensive chemical analysis and optimization of the gel formulation. Some insights into the physicochemical mechanisms were obtained and are discussed in this paper.