Effect of IV Administration of a Gadolinium-Based Contrast Agent on Breast Diffusion-Tensor Imaging.

OBJECTIVE. The purpose of this study was to quantify changes in diffusion-tensor imaging (DTI) parameters before and after IV administration of a gadolinium-based contrast agent (GBCA) and explore the influence of those parameters on breast cancer diagnosis. SUBJECTS AND METHODS. A prospective cohort of 26 women with BI-RADS categories 0, 4, 5, or 6 underwent 3-T breast MRI with sequential DTI before GBCA administration and immediately after. Quantitative image analysis using dedicated DTI software yielded parametric DTI maps of each directional diffusion coefficient (DDC), mean diffusivity, and maximal anisotropy of the lesions and normal tissue. The color maps were evaluated and the lesion DTI parameters were compared before and after GBCA administration using appropriate statistical tests. RESULTS. Of the cohort, 58% had cancer (13 infiltrating ductal carcinoma, two ductal carcinoma in situ) and 42% had benign or normal results. All breast cancers were visually detected in the DDC λ1 maps before and after GBCA administration. Mean cancer size derived from λ1 maps before GBCA administration was 15.3 mm (range, 3.3-72.3 mm), and was not statistically significantly different from the size derived after GBCA administration of 17.3 mm (range, 3.9-71.0 mm). After GBCA administration, the cancers exhibited statistically significantly lower DDCs, mean diffusivity, and b0 intensity (p < 0.05), and no change in maximal anisotropy compared with before GBCA administration, whereas these parameters in normal and benign lesions did not change significantly after GBCA administration. The mean AUC values before and after GBCA administration, ranging from 0.735 to 0.985 and from 0.867 to 0.990, respectively, were not statistically significantly different for all parameters aside from λ3. CONCLUSION. Diagnostic accuracy using DTI was equivalent before and after GBCA administration, despite a change in the values of the DTI parameters. However, the limitations in standardization of contrast enhancement implies that unenhanced diffusion measurements should be preferred.

Monitoring In-Vivo the Mammary Gland Microstructure during Morphogenesis from Lactation to Post-Weaning Using Diffusion Tensor MRI.

Lactation and the return to the pre-conception state during post-weaning are regulated by hormonal induced processes that modify the microstructure of the mammary gland, leading to changes in the features of the ductal / glandular tissue, the stroma and the fat tissue. These changes create a challenge in the radiological workup of breast disorder during lactation and early post-weaning. Here we present non-invasive MRI protocols designed to record in vivo high spatial resolution, T2-weighted images and diffusion tensor images of the entire mammary gland. Advanced imaging processing tools enabled tracking the changes in the anatomical and microstructural features of the mammary gland from the time of lactation to post-weaning. Specifically, by using diffusion tensor imaging (DTI) it was possible to quantitatively distinguish between the ductal / glandular tissue distention during lactation and the post-weaning involution. The application of the T2-weighted imaging and DTI is completely safe, non-invasive and uses intrinsic contrast based on differences in transverse relaxation rates and water diffusion rates in various directions, respectively. This study provides a basis for further in-vivo monitoring of changes during the mammary developmental stages, as well as identifying changes due to malignant transformation in patients with pregnancy associated breast cancer (PABC).

Can diffusion tensor anisotropy indices assist in breast cancer detection?

PURPOSE: To evaluate whether the various anisotropy indices derived from breast diffusion tensor imaging (DTI) can characterize the healthy breast structure and differentiate cancer from normal breast tissue. MATERIALS AND METHODS: Six healthy volunteers and retrospectively selected 24 breast cancer patients were imaged at 3T. DTI included two b-values 0 and 700 sec/mm2 with 20-64 gradient directions and TE of 120 or 90 msec. The normalized anisotropy indices: fractional anisotropy (FA), relative anisotropy (RA), and 1-volume ratio (1-VR), as well as the absolute maximal anisotropy index (λ1 -λ3 ) were compared. RESULTS: The spatial distribution of the various anisotropy indices in healthy volunteers exhibited a high congruence (Pearson correlation coefficients range: 0.79-1.0). All indices showed a statistically significant reduction (P < 0.001) following shortening of the diffusion time. Significantly lower λ1 -λ3 values were found in cancers as compared to normal breast tissue (P < 6.0 × 10-7 ), while the values of the normalized indices in cancers were not significantly different from those in normal breast tissue (P < 0.65 for FA, P < 0.6 for RA, and P < 0.2 for 1-VR). The contrast-to-noise ratio of λ1 -λ3 was significantly higher (P < 0.001) than those of the normalized anisotropy indices, and the area under the curve in a receiver operating characteristic analysis exhibited the highest value for λ1 -λ3 (0.89 ± 0.04 vs. 0.51-0.54 for the other anisotropy indices). CONCLUSION: Water diffusion anisotropy in the healthy breast can be similarly mapped by the normalized indices and by λ1 -λ3 . However, the normalized anisotropy indices fail to differentiate cancer from normal breast tissue, whereas λ1 -λ3 can assist in differentiating cancer from normal breast tissue. J. Magn. Reson. Imaging 2016;44:1624-1632.

Diffusion-tensor MR imaging of the breast: hormonal regulation.

PURPOSE: To investigate the parameters obtained with magnetic resonance (MR) diffusion-tensor imaging (DTI) of the breast throughout the menstrual cycle phases, during lactation, and after menopause, with and without hormone replacement therapy (HRT). MATERIALS AND METHODS: All protocols were approved by the internal review board, and signed informed consent was obtained from all participants. Forty-five healthy volunteers underwent imaging by using T2-weighted and DTI MR sequences at 3 T. Premenopausal volunteers (n = 16) underwent imaging weekly, four times during one menstrual cycle. Postmenopausal volunteers (n = 19) and lactating volunteers (n = 10) underwent imaging once. The principal diffusion coefficients (λ1, λ2, and λ3), apparent diffusion coefficient (ADC), fractional anisotropy (FA), and maximal anisotropy (λ1-λ3) were calculated pixel by pixel for the fibroglandular tissue in the entire breast. RESULTS: In all premenopausal volunteers, the DTI parameters exhibited high repeatability, remaining almost equal along the menstrual cycle, with a low mean within-subject coefficient of variance of λ1, λ2, λ3, and ADC (1%-2% for all) and FA (5%), as well as a high intraclass correlation of 0.92-0.98. The diffusion coefficients were significantly lower (a) in the group without HRT use as compared with the group with HRT use (P < .01) and premenopausal volunteers (P < .01) and (b) in the lactating volunteers as compared with the premenopausal volunteers (P < .005). No significant differences in DTI parameters were found between premenopausal volunteers free of oral contraceptives and those who used oral contraceptives (P = .28-0.82) and between premenopausal volunteers and postmenopausal volunteers who used HRT (P = .31-0.93). CONCLUSION: DTI parameters are not sensitive to menstrual cycle changes, while menopause, long-term HRT, and presence of milk in lactating women affected the DTI parameters. Therefore, the timing for performing breast DTI is not restricted throughout the menstrual cycle, whereas the modulations in diffusion parameters due to HRT and lactation should be taken into account in DTI evaluation.

Tracking the mammary architectural features and detecting breast cancer with magnetic resonance diffusion tensor imaging.

Breast cancer is the most common cause of cancer among women worldwide. Early detection of breast cancer has a critical role in improving the quality of life and survival of breast cancer patients. In this paper a new approach for the detection of breast cancer is described, based on tracking the mammary architectural elements using diffusion tensor imaging (DTI). The paper focuses on the scanning protocols and image processing algorithms and software that were designed to fit the diffusion properties of the mammary fibroglandular tissue and its changes during malignant transformation. The final output yields pixel by pixel vector maps that track the architecture of the entire mammary ductal glandular trees and parametric maps of the diffusion tensor coefficients and anisotropy indices. The efficiency of the method to detect breast cancer was tested by scanning women volunteers including 68 patients with breast cancer confirmed by histopathology findings. Regions with cancer cells exhibited a marked reduction in the diffusion coefficients and in the maximal anisotropy index as compared to the normal breast tissue, providing an intrinsic contrast for delineating the boundaries of malignant growth. Overall, the sensitivity of the DTI parameters to detect breast cancer was found to be high, particularly in dense breasts, and comparable to the current standard breast MRI method that requires injection of a contrast agent. Thus, this method offers a completely non-invasive, safe and sensitive tool for breast cancer detection.

Diffusion tensor magnetic resonance imaging of the pancreas.

PURPOSE: To develop a diffusion-tensor-imaging (DTI) protocol that is sensitive to the complex diffusion and perfusion properties of the healthy and malignant pancreas tissues. MATERIALS AND METHODS: Twenty-eight healthy volunteers and nine patients with pancreatic-ductal-adenocacinoma (PDAC), were scanned at 3T with T2-weighted and DTI sequences. Healthy volunteers were also scanned with multi-b diffusion-weighted-imaging (DWI), whereas a standard clinical protocol complemented the PDAC patients' scans. Image processing at pixel resolution yielded parametric maps of three directional diffusion coefficients λ1, λ2, λ3, apparent diffusion coefficient (ADC), and fractional anisotropy (FA), as well as a λ1-vector map, and a main diffusion-direction map. RESULTS: DTI measurements of healthy pancreatic tissue at b-values 0,500 s/mm² yielded: λ1 = (2.65±0.35)×10⁻³, λ2 = (1.87±0.22)×10⁻³, λ3 = (1.20±0.18)×10⁻³, ADC = (1.91±0.22)×10⁻³ (all in mm²/s units) and FA = 0.38±0.06. Using b-values of 100,500 s/mm² led to a significant reduction in λ1, λ2, λ3 and ADC (p<.0001) and a significant increase (p<0.0001) in FA. The reduction in the diffusion coefficients suggested a contribution of a fast intra-voxel-incoherent-motion (IVIM) component at b≤100 s/mm², which was confirmed by the multi-b DWI results. In PDACs, λ1, λ2, λ3 and ADC in both 0,500 s/mm² and 100,500 s/mm² b-values sets, as well as the reduction in these diffusion coefficients between the two sets, were significantly lower in comparison to the distal normal pancreatic tissue, suggesting higher cellularity and diminution of the fast-IVIM component in the cancer tissue. CONCLUSION: DTI using two reference b-values 0 and 100 s/mm² enabled characterization of the water diffusion and anisotropy of the healthy pancreas, taking into account a contribution of IVIM. The reduction in the diffusion coefficients of PDAC, as compared to normal pancreatic tissue, and the smaller change in these coefficients in PDAC when the reference b-value was modified from 0 to 100 s/mm², helped identifying the presence of malignancy.

Parametric diffusion tensor imaging of the breast.

OBJECTIVES: To investigate the ability of parametric diffusion tensor imaging (DTI), applied at 3 Tesla, to dissect breast tissue architecture and evaluate breast lesions. MATERIALS AND METHODS: All protocols were approved and a signed informed consent was obtained from all subjects. The study included 21 healthy women, 26 women with 33 malignant lesions, and 14 women with 20 benign lesions. Images were recorded at 3 Tesla with a protocol optimized for breast DTI at a spatial resolution of 1.9 × 1.9 × (2-2.5) mm3. Image processing algorithms and software, applied at pixel resolution, yielded vector maps of prime diffusion direction and parametric maps of the 3 orthogonal diffusion coefficients and of the fractional anisotropy and maximal anisotropy. RESULTS: The DTI-derived vector maps and parametric maps revealed the architecture of the entire mammary fibroglandular tissue and allowed a reliable detection of malignant lesions. Cancer lesions exhibited significantly lower values of the orthogonal diffusion coefficients, λ1, λ2, λ3, and of the maximal anisotropy index λ1-λ3 as compared with normal breast tissue (P < 0.0001) and to benign breast lesions (P < 0.0009 and 0.004, respectively). Maps of λ1 exhibited the highest contrast-to-noise ratio enabling delineation of the cancer lesions. These maps also provided high sensitivity/specificity of 95.6%/97.7% for differentiating cancers from benign lesions, which were similar to the sensitivity/specificity of dynamic contrast-enhanced magnetic resonance imaging of 94.8%/92.9%. Maps of λ1-λ3 provided a secondary independent diagnostic parameter with high sensitivity of 92.3%, but low specificity of 69.5% for differentiating cancers from benign lesions. CONCLUSION: Mapping the diffusion tensor parameters at high spatial resolution provides a potential novel means for dissecting breast architecture. Parametric maps of λ1 and λ1-λ3 facilitate the detection and diagnosis of breast cancer.

Vascular perfusion of human lung cancer in a rat orthotopic model using dynamic contrast-enhanced magnetic resonance imaging.

Lung cancer is the leading cause of death among cancers. Early detection and diagnosis present a major goal in the efforts to improve survival rates of lung cancer patients. Changes in angiogenic activity and microvascular perfusion properties in cancers can serve as markers of malignancy. The aim of this study was to employ MRI means to measure the microvascular perfusion parameters of orthotopic nonsmall cell lung cancer, using the experimental rat model. Anatomical and dynamic contrast-enhanced lung images were acquired at high spatial resolution, and registered and analyzed, pixel by pixel and globally, by means of a model-based algorithm. The MRI output yielded color-coded parametric images of the influx and efflux transcapillary transfer constants that indicated rapid microvascular perfusion. The transfer constants were about 1 order of magnitude higher than those found in other tumors or in nonorthotopic lung cancer, with the influx constant median value of 0.42 min(-1) and the efflux constant median value of 1.61 min(-1). The rapid perfusion was in accord with the immunostaining of the capillaries, which suggested the tumor exploitation of the existing alveolar vessels. The results showed that high resolution, dynamic, contrast-enhanced MRI is an effective tool for the quantitative measurement of spatial and temporal changes in lung cancer perfusion and vasculature.

Clinical testing of high-spatial-resolution parametric contrast-enhanced MR imaging of the breast.

OBJECTIVE: We performed a prospective clinical test of a high-spatial-resolution model-based parametric method for diagnosis of breast lesions detected on contrast-enhanced MR imaging. SUBJECTS AND METHODS: Fifty-seven women with 68 pathologically confirmed breast lesions were imaged (45 masses, 23 microcalcifications). Seven consecutive 2-min three-dimensional gradient-recalled echo acquisitions were performed after suitably timed gadopentetate dimeglumine injections. We derived a composite parametric image from three judiciously selected time points (three-time-point method), using a model-based kinetic algorithm. In this composite image, color brightness and hue signify contrast uptake and washout characteristics related to the product of microvessel surface area and permeability, as well as to the extracellular volume fraction. The reviewer was provided with the slice location of lesions, but with no other radiographic or clinical information. The reviewer then classified the lesions as benign or malignant using a 5-step receiver operating characteristic scale. RESULTS: Observers using the three-time-point method correctly diagnosed 27 of 31 malignant and 31 of 37 benign lesions (sensitivity, 87%; specificity, 84%). The area under the receiver operating characteristic curve was 0.911. False-negative results were found for three patients with low- to intermediate-grade ductal carcinoma in situ and one patient with 5-mm invasive ductal cancer. For the 45 solid lesions, sensitivity and specificity were 96% and 82%, respectively. CONCLUSION: Application of the three-time-point method permitted, in most cases, differentiation of malignant and benign lesions, even in the presence of complex breast enhancement patterns. Sensitivity for solid tumors was higher than for ductal carcinoma in situ.