Dynamic Contrast Agent-enhanced Magnetic Resonance Imaging Research Articles

The potential of hyperpolarized 13C magnetic resonance spectroscopy to monitor the effect of combretastatin based vascular disrupting agents

Background: Targeting tumor vasculature with vascular disrupting agents (VDAs) results in substantial cell death that precede tumor shrinkage. Here, we investigate the potential of hyperpolarized magnetic resonance spectroscopy (HPMRS) to monitor early metabolic changes associated with VDA treatment.Methods: Mice bearing C3H mammary carcinomas were treated with the VDAs combretastatin-A4-phosphate (CA4P) or the analog OXi4503, and HPMRS was performed following [1-13C]pyruvate administration. Similarly, treated mice were positron emission tomography (PET) scanned following administration of the glucose analog FDG. Finally, metabolic imaging parameters were compared to tumor regrowth delay and measures of vascular damage, derived from dynamic contrast-agent enhanced magnetic resonance imaging (DCE-MRI) and histology.Results: VDA-treatment impaired tumor perfusion (histology and DCE-MRI), reduced FDG uptake, increased necrosis, and slowed tumor growth. HPMRS, revealed that the [1-13C]pyruvate-to-[1-13C]lactate conversion remained unaltered, whereas [1-13C]lactate-to-[13C]bicarbonate (originating from respiratory CO2) ratios increased significantly following treatment.Conclusions: DCE-MRI and FDG-PET revealed loss of vessel functionality, impaired glucose delivery and reduced metabolic activity prior to cell death. [1-13C]lactate-to-[13C]bicarbonate ratios increased significantly during treatment, indicating a decline in respiratory activity driven by the onset of hypoxia. HPMRS is promising for early detection of metabolic stress inflicted by VDAs, which cannot easily be inferred based on blood flow measurements.

Surveillance of Women with the BRCA1 or BRCA2 Mutation by Using Biannual Automated Breast US, MR Imaging, and Mammography.

Purpose To evaluate a multimodal surveillance regimen including yearly full-field digital (FFD) mammography, dynamic contrast agent-enhanced (DCE) magnetic resonance (MR) imaging, and biannual automated breast (AB) ultrasonography (US) in women with BRCA1 and BRCA2 mutations. Materials and Methods This prospective multicenter trial enrolled 296 carriers of the BRCA mutation (153 BRCA1 and 128 BRCA2 carriers, and 15 women with first-degree untested relatives) between September 2010 and November 2012, with follow-up until November 2015. Participants underwent 2 years of intensified surveillance including biannual AB US, and routine yearly DCE MR imaging and FFD mammography. The surveillance performance for each modality and possible combinations were determined. Results Breast cancer was screening-detected in 16 women (age range, 33-58 years). Three interval cancers were detected by self-examination, all in carriers of the BRCA1 mutation under age 43 years. One cancer was detected in a carrier of the BRCA1 mutation with a palpable abnormality in the contralateral breast. One incidental breast cancer was detected in a prophylactic mastectomy specimen. Respectively, sensitivity of DCE MR imaging, FFD mammography, and AB US was 68.1% (14 of 21; 95% confidence interval [CI]: 42.9%, 85.8%), 37.2% (eight of 21; 95% CI: 19.8%, 58.7%), and 32.1% (seven of 21; 95% CI: 16.1%, 53.8%); specificity was 95.0% (643 of 682; 95% CI: 92.7%, 96.5%), 98.1% (638 of 652; 95% CI: 96.7%, 98.9%), and 95.1% (1030 of 1088; 95% CI: 93.5%, 96.3%); cancer detection rate was 2.0% (14 of 702), 1.2% (eight of 671), and 1.0% (seven of 711) per 100 women-years; and positive predictive value was 25.2% (14 of 54), 33.7% (nine of 23), and 9.5% (seven of 68). DCE MR imaging and FFD mammography combined yielded the highest sensitivity of 76.3% (16 of 21; 95% CI: 53.8%, 89.9%) and specificity of 93.6% (643 of 691; 95% CI: 91.3%, 95.3%). AB US did not depict additional cancers. FFD mammography yielded no additional cancers in women younger than 43 years, the mean age at diagnosis. In carriers of the BRCA2 mutation, sensitivity of FFD mammography with DCE MR imaging surveillance was 90.9% (10 of 11; 95% CI: 72.7%, 100%) and 60.0% (six of 10; 95% CI: 30.0%, 90.0%) in carriers of the BRCA1 mutation because of the high interval cancer rate in carriers of the BRCA1 mutation. Conclusion AB US may not be of added value to yearly FFD mammography and DCE MR imaging surveillance of carriers of the BRCA mutation. Study results suggest that carriers of the BRCA mutation younger than 40 years may not benefit from FFD mammography surveillance in addition to DCE MR imaging. © RSNA, 2017 Online supplemental material is available for this article.

Reduction of Longitudinal Vertebral Blood Perfusion and Its Likely Causes: A Quantitative Dynamic Contrast-enhanced MR Imaging Study of a Rat Osteoporosis Model.

Purpose To determine the longitudinal relationships among lumbar vertebral blood perfusion, bone mass, and marrow adipose tissue in a rat osteoporosis model after ovariectomy by using quantitative dynamic contrast agent-enhanced (DCE) magnetic resonance (MR) imaging, microcomputed tomography (micro-CT), and proton MR spectroscopy. Materials and Methods In this animal review committee-approved study, lumbar vertebrae were evaluated through MR spectroscopy, quantitative DCE MR imaging, micro-CT, and histopathologic analysis, and blood was examined at 0, 2, 6, 10, 14, 18, and 24 weeks after ovariectomy consisting of exposure of the ovaries but no excision (n = 35) or sham operation, defined as exposure of the ovaries but no excision (n = 35). Differences in the parameters of these examinations between two groups at the same time point were analyzed by an independent-sample t test. Results Significantly reduced volume transfer constant (Ktrans) and volume of extravascular extracellular space per unit volume of tissue (week 2 and 10, respectively; P = .036 and P = .014, respectively), decreased bone mineral density (week 2; P = .014), and increased fat fraction (week 6; P = .036) in the ovariectomy group were observed, compared with those in the sham group. Vascular endothelial growth factor and microvessel density values of the ovariectomy group decreased significantly compared with those of the sham group from weeks 18 (P = .005) and 14 (P = .018), respectively. Transmission electron microscopy revealed tighter gaps among vascular endothelial cells and more marrow fibrosis in the ovariectomy group. Conclusion Quantitative DCE MR imaging can directly reflect marrow perfusion. Ktrans is a promising parameter to demonstrate early reduced marrow perfusion. Enhanced vasoconstriction and tightened gaps among vascular endothelial cells may be the likely causes in the initial stage of osteoporosis. Increased marrow adipose tissue, decreased microvessel density, and increased marrow fibrosis may aggravate marrow ischemia in the late stage of osteoporosis. © RSNA, 2016 Online supplemental material is available for this article.

A Simplified Approach to Measure the Effect of the Microvasculature in Diffusion-weighted MR Imaging Applied to Breast Tumors: Preliminary Results.

Purpose To evaluate the relative change of the apparent diffusion coefficient (ADC) at low- and medium-b-value regimens as a surrogate marker of microcirculation, to study its correlation with dynamic contrast agent-enhanced (DCE) magnetic resonance (MR) imaging-derived parameters, and to assess its potential for differentiation between malignant and benign breast tumors. Materials and Methods Ethics approval and informed consent were obtained. From May 2013 to June 2015, 61 patients diagnosed with either malignant or benign breast tumors were prospectively recruited. All patients were scanned with a 3-T MR imager, including diffusion-weighted imaging (DWI) and DCE MR imaging. Parametric analysis of DWI and DCE MR imaging was performed, including a proposed marker, relative enhanced diffusivity (RED). Spearman correlation was calculated between DCE MR imaging and DWI parameters, and the potential of the different DWI-derived parameters for differentiation between malignant and benign breast tumors was analyzed by dividing the sample into equally sized training and test sets. Optimal cut-off values were determined with receiver operating characteristic curve analysis in the training set, which were then used to evaluate the independent test set. Results RED had a Spearman rank correlation of 0.61 with the initial area under the curve calculated from DCE MR imaging. Furthermore, RED differentiated cancers from benign tumors with an overall accuracy of 90% (27 of 30) on the test set with 88.2% (15 of 17) sensitivity and 92.3% (12 of 13) specificity. Conclusion This study presents promising results introducing a simplified approach to assess results from a DWI protocol sensitive to the intravoxel incoherent motion effect by using only three b values. This approach could potentially aid in the differentiation, characterization, and monitoring of breast pathologies. © RSNA, 2016 Online supplemental material is available for this article.

Intravoxel Incoherent Motion Diffusion-weighted Imaging of Multiple Myeloma Lesions: Correlation with Whole-Body Dynamic Contrast Agent-enhanced MR Imaging.

To correlate intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) parameters with the enhancement patterns of bone marrow and focal lesion obtained on whole-body (WB) dynamic contrast agent-enhanced (DCE) magnetic resonance (MR) images in patients with stage-III multiple myeloma (MM) before and after systemic therapy. Twenty-seven patients with MM were retrospectively included in this institutional review board-approved study. Requirement for written informed consent was waived. All patients underwent WB DCE MR imaging before treatment and 18 patients underwent repeat MR imaging 3 months after treatment. A transverse IVIM DWI sequence with 10 b values (0, 10, 20, 30, 50, 80, 100, 200, 400, and 800 sec/mm(2)) was acquired within bone marrow and focal lesions. The IVIM parameters (perfusion fraction [f], molecular diffusion coefficient [D], and perfusion-related D [D*]) and apparent diffusion coefficient (ADC) were extracted for both focal lesions and bone marrow and correlated with focal lesions and maximal bone marrow enhancement (BMEmax) (Spearman correlation coefficient) at baseline and at follow-up (Wilcoxon signed-rank test). D and ADC values positively correlated with BMEmax (r = 0.7, P < .001; and r = 0.455, P = .0435, respectively). Patients with increased BMEmax showed significantly increased ADC and D within bone marrow versus patients who did not have increased BMEmax (ADC, 0.67 × 10(-3) mm(2)/sec vs 0.54 × 10(-3) mm(2)/sec, P = .03; D, 0.58 × 10(-3) mm(2)/sec vs 0.42 × 10(-3) mm(2)/sec, P < .001). Within focal lesions, f was the maximum in lesions that showed enhancement followed by washout. After treatment in good responders, the significant decrease in maximal enhancement value of focal lesions (baseline vs after treatment, 213.9% ± 78.7 [standard deviation] vs 131% ± 53.6, respectively; P < .001) was accompanied by a significant decrease in f (baseline vs after treatment, 11% ± 3.8 vs 5.8% ± 4.7, respectively; P < .001). Diffuse bone marrow involvement is associated with increased D. Hypervascular focal lesions with high maximal enhancement value of focal lesions also show high f value. Likewise, the decreased maximal enhancement value of focal lesions after treatment is accompanied by decreased f.

Survival Outcomes of Breast Cancer Patients Who Receive Neoadjuvant Chemotherapy: Association with Dynamic Contrast-enhanced MR Imaging with Computer-aided Evaluation

To retrospectively evaluate whether dynamic contrast agent-enhanced (DCE) magnetic resonance (MR) imaging parameters assessed by a computer-aided evaluation program are associated with recurrence-free and overall survival in breast cancer patients who received neoadjuvant chemotherapy (NAC). This study was institutional review board approved and informed consent was waived. Between January 2007 and December 2009, 187 consecutive women (mean age, 46.6 years; range, 24-78 years) who had undergone NAC, DCE MR imaging before and after NAC, and surgery for invasive breast cancers (mean size, 5.0 cm; range, 2.0-14.8 cm on surgical histologic analysis) were identified. The tumor size, volume, and kinetic parameters (persistent, plateau, or washout components) were measured with a computer-aided evaluation program on DCE MR images before and after NAC, and their percentage changes were calculated. The Cox proportional hazards model was used to determine the association between DCE MR imaging parameters and recurrence-free survival and overall survival after controlling for clinical-pathologic variables. There were 50 events, including 38 recurrences (29 distant, six local, and three both) and 12 deaths, at a mean follow-up of 47.4 months. At multivariate analysis, a smaller reduction in tumor volume (recurrence-free survival hazard ratio, 5.75; 95% confidence interval: 1.14, 8.64; and overall survival hazard ratio, 2.12; 95% confidence interval: 1.08, 5.69) and a smaller reduction in washout component (recurrence-free survival hazard ratio, 1.15; 95% CI: 1.06, 1.55; and overall survival hazard ratio, 1.26; 95% confidence interval: 1.03, 1.52) after NAC were independent significant variables for worse recurrence-free survival and overall survival. Smaller reduction in tumor volume and a smaller reduction in washout component on DCE MR images assessed with computer-aided evaluation after NAC were independent parameters of worse recurrence-free survival and overall survival in breast cancer patients who received NAC.

The Added Role of MR Imaging in Treatment Stratification of Patients with Gynecologic Malignancies: What the Radiologist Needs to Know

Many treatment options are available to patients with endometrial, cervical, or ovarian cancer. Magnetic resonance (MR) imaging plays an important role in the patient journey from the initial evaluation of the extent of the disease to appropriate treatment selection and follow-up. The purpose of this review is to highlight the added role of MR imaging in the treatment stratification and overall care of patients with endometrial, cervical, or ovarian cancer. Several MR imaging techniques used in evaluation of patients with gynecologic malignancies are described, including both anatomic MR imaging sequences (T1- and T2-weighted sequences) and pulse sequences that characterize tissue on the basis of physiologic features (diffusion-weighted MR imaging), dynamic contrast agent-enhanced MR imaging, and MR spectroscopy. MR imaging findings corresponding to the 2009 revised International Federation of Gynecology and Obstetrics staging of gynecologic malignancies are also described in detail, highlighting possible pearls and pitfalls of staging. With the growing role of the radiologist as a core member of the multidisciplinary treatment planning team, it is crucial for imagers to recognize that MR imaging has become central in tailoring treatment options and therapy in patients with gynecologic malignancies.

MR Imaging of Treated Prostate Cancer

Many management options are available to patients with newly diagnosed prostate cancer. Magnetic resonance (MR) imaging plays an important role in initial staging of prostate cancer, but it also aids in tumor detection when there is clinical or biochemical suspicion of residual or recurrent disease after treatment. The purpose of this review is to describe the normal appearances of the prostatic region after different kinds of treatment for prostate cancer and to discuss how these appearances differ from those of recurrent and residual disease. Several MR imaging techniques used in evaluating patients with prostate cancer are described, including conventional MR imaging sequences (mainly T1- and T2-weighted sequences), MR spectroscopic imaging, diffusion-weighted imaging, and dynamic contrast agent-enhanced MR imaging. Clinical considerations, together with the different approaches for interpreting serum prostate-specific antigen values in the posttreatment setting, are also presented. All forms of treatment alter the MR imaging features of the prostatic region to a greater or lesser extent, and it is important to be able to recognize expected posttreatment appearances and distinguish them from the features of recurrent or residual cancer to aid subsequent clinical management.

Detection of tumor response to a vascular disrupting agent by hyperpolarized 13C magnetic resonance spectroscopy.

Nuclear spin hyperpolarization can dramatically increase the sensitivity of the (13)C magnetic resonance experiment, allowing dynamic measurements of the metabolism of hyperpolarized (13)C-labeled substrates in vivo. Here, we report a preclinical study of the response of lymphoma tumors to the vascular disrupting agent (VDA), combretastatin-A4-phosphate (CA4P), as detected by measuring changes in tumor metabolism of hyperpolarized [1-(13)C]pyruvate and [1,4-(13)C(2)]fumarate. These measurements were compared with dynamic contrast agent-enhanced magnetic resonance imaging (DCE-MRI) measurements of tumor vascular function and diffusion-weighted MRI (DW-MRI) measurements of the tumor cell necrosis that resulted from subsequent loss of tumor perfusion. The rate constant describing flux of hyperpolarized (13)C label between [1-(13)C]pyruvate and lactate was decreased by 34% within 6 hours of CA4P treatment and remained at this lower level at 24 hours. The rate constant describing production of labeled malate from hyperpolarized [1,4-(13)C(2)]fumarate increased 1.6-fold and 2.5-fold at 6 and 24 hours after treatment, respectively, and correlated with the degree of necrosis detected in histologic sections. Although DCE-MRI measurements showed a substantial reduction in perfusion at 6 hours after treatment, which had recovered by 24 hours, DW-MRI showed no change in the apparent diffusion coefficient of tumor water at 6 hours after treatment, although there was a 32% increase at 24 hours (P < 0.02) when regions of extensive necrosis were observed by histology. Measurements of hyperpolarized [1-(13)C]pyruvate and [1,4-(13)C(2)]fumarate metabolism may provide, therefore, a more sustained and sensitive indicator of response to a VDA than DCE-MRI or DW-MRI, respectively.