Predictors of dopamine agonist resistance in prolactinoma patients.

BACKGROUND: Surgical resection of prolactinomas resistant to dopamine agonists is frequently incomplete due to fibrotic changes of the tumour under pharmacological therapy. In order to identify a subgroup of patients who may benefit from early surgery, we thought to investigate possible predictive factors of pharmacological resistance of prolactinomas to dopamine agonists. METHODS: We retrospectively analyzed a database of a Belgian tertiary reference center for patients with pituitary tumours from 2014 to 2016. The groups of interest were patients with dopamine agonist responsive and resistant prolactinomas. The possible predictive factors, including MRI findings, endocrinological parameters, response of tumour and patient factors for dopamine agonist resistance were investigated. RESULTS: We included 69 patients of whom 52 were women (75,4%) and 17 were men (24,6%). Rate of dopamine agonist resistance was 15.9%. We identified four significant predictors of dopamine agonist resistance: male gender, a large tumour volume, prolonged time to prolactin normalization and presence of a cystic, hemorrhagic and/or necrotic component. In addition, symptoms due to mass effect, high baseline prolactin level and a high contrast capture on MRI are factors that can be taken into consideration. CONCLUSION: We identified predictive factors for pharmacological resistance and developed a scoring system for patient specific prediction of resistance to dopamine agonists. This scoring system may have impact on the timing and decision of surgery in prolactinoma patients after further prospective evaluation.

Quantification of cerebral tumour blood flow and permeability with T1-weighted dynamic contrast enhanced MRI: a feasibility study.

OBJECTIVES: Recently, T1-weighted DCE-MRI was proposed as an alternative to T2*-weighted DSC-MRI for the quantification of perfusion and permeability in brain tumors. The aim of the present feasibility study was to explore the clinical potential of the technique in different tumor types using a case-based review of initial results. PATIENTS AND METHODS: The method for data analysis was adapted from cerebral perfusion CT and applied in this study to a small group of patients with grade IV glioma and other brain tumors. The possible use of the proposed methodology was also explored for characterizing, following-up and planning the therapy of brain tumors. RESULTS: Parametric maps clearly differentiated tumor from the surrounding brain tissue, and also distinguished areas within the tumor presenting with different characteristics, thereby allowing identification of significant target areas for biopsy and/or treatment. Differences in cerebral blood flow (CBF) and lower extraction fractions (E) were observed in various tumors. Progression from a grade II to grade IV glioma over the course of a year was characterized by an increase in CBF and a decrease in E. CONCLUSION: DCE-MRI-based quantitative perfusion and permeability may be helpful for tumor-grade characterization, biopsy guidance, radiotherapy planning, radiotherapy monitoring and clinical follow-up, thereby improving the non-invasive characterization of brain tumors.

Assessment of tumor blood flow in breast tumors with T1-dynamic contrast-enhanced MR imaging: impact of dose reduction and the use of a prebolus technique on diagnostic efficacy.

PURPOSE: To prospectively evaluate whether dose reduction and the application of a prebolus technique can effectively alleviate signal saturation effects in T1 dynamic contrast enhanced (T1-DCE) magnetic resonance imaging (MRI) data in breast tumors and lead to increased diagnostic efficacy of the regional tumor blood flow (TBF) values obtained with deconvolution of T1-DCE MRI data. MATERIALS AND METHODS: After obtaining informed consent, 23 women (32-80 years) with histologically proven breast tumors underwent MR mammography that included a whole-breast T1 DCE sequence. In the slice where the tumor enhanced maximally, a prebolus protocol was applied. One mL of Gd-DTPA solution at 2 mL/s was injected at the beginning of a dynamic axial single slice inversion-prepared turbo field echo acquisition. At the 400th dynamic, a high dose of either 20 mL (15 patients) or 10 mL (8 patients) of contrast agent was injected at 2 mL/s and a further 400 dynamics were acquired. From the aortic prebolus curve an arterial input function (AIF) was reconstructed by time-shifting and adding the prebolus data. The relative enhancement time course from the tumor region of interest was deconvolved with the reconstructed AIF to generate the impulse response function, the maximum of which yielded the TBF. The institutional ethical committee approved the study. RESULTS: Reducing the contrast dose by a factor of 2 led to an increase in diagnostic contrast for the TBF values of malignant and benign tumors by a factor of slightly more than 2. Addition of the prebolus technique improved this further by 45%. receiver operating characteristic analysis showed a significant increase of diagnostic yield related to the combined use of a prebolus and minimal dose. CONCLUSION: Using a prebolus approach provides an estimate of the unsaturated AIF, while reduction of the high-dose bolus minimizes possible saturation effects in the tumor time course.

Deconvolution-based dynamic contrast-enhanced MR imaging of breast tumors: correlation of tumor blood flow with human epidermal growth factor receptor 2 status and clinicopathologic findings--preliminary results.

PURPOSE: To prospectively determine whether breast carcinomas possess characteristic values of tumor blood flow (TBF) that correlate with pathologic and molecular prognostic markers. MATERIALS AND METHODS: The institutional ethics committee approved this study. After informed consent was obtained, 57 women (age range, 31-80 years) with histologically proved breast cancer underwent routine magnetic resonance (MR) mammography, which included a whole-breast dynamic contrast material-enhanced (DCE) sequence. A second contrast material bolus was injected during dynamic single-section turbo field-echo imaging of the section where the lesion was maximally enhanced. The relative signal intensity changes were deconvolved in a pixelwise fashion to yield the TBF. Formalin-fixed paraffin-embedded tumor specimens on slides were evaluated for histologic size and grade, as well as for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) protein. In patients with a HER2 protein score of 2+ or 3+, HER2 gene status was assessed. For all prognostic parameters, the Mann-Whitney U test was used to compare median TBF in the HER2-positive group with that in the HER2-negative group. RESULTS: Significantly higher TBF was observed in tumors larger than 2 cm in diameter and in PR-negative and HER2 gene-amplified tumors (P < .05). In the HER2-positive and HER2-negative groups, ER-positive PR-positive tumors had a lower median TBF than did ER-negative PR-negative tumors, and the difference was significant in the HER2-positive group (P < .05). CONCLUSION: Pixelwise deconvolution analysis of DCE MR data in patients with breast cancer can provide preoperative information regarding TBF. These results also support the hypothesis that there is increased TBF in HER2-positive tumors.

Pathogenesis of venous stroke: evaluation with diffusion- and perfusion-weighted MRI.

Previous reports have demonstrated the diagnostic usefulness of diffusion- and perfusion-weighted magnetic resonance imaging (MRI) in the evaluation of cerebral venous thrombosis. However, the explanations ascribed for the pathophysiologic mechanisms of venous stroke in these reports were conflicting. Earlier reports supported prominent vasogenic edema associated with mild cytotoxic edema as the potential pathophysiologic mechanism. More recently, a few reports have found cytotoxic edema as the cause for venous stroke. The purpose of this report is to review the pathogenesis of cerebral venous thrombosis after taking into consideration the results of MRI findings. We report two cases of cerebral venous infarction, which had worsening symptoms and signs that resolved after intravenous heparin therapy. In both cases, findings on diffusion-weighted and perfusion-weighted MRI images were compatible with vasogenic edema and viable neuronal tissue. Both the patients recovered without any significant residual sequel. We support the hypothesis that in the pathogenesis of venous stroke vasogenic edema is the initial event, which may or may not be followed by cytotoxic edema eventually evolving to an infarction.

Age dependence of T1 perfusion MRI-based hemodynamic parameters in human kidneys.

PURPOSE: To determine the association between renal cortical perfusion parameters from T1-DCE magnetic resonance imaging (MRI) and age in human kidney. MATERIALS AND METHODS: Thirty-five patients (mean age: 53 years, SD = 15 years) were imaged using inversion recovery (IR)-prepared FLASH (pulse repetition time [TR] = 4.4 msec, echo time [TE] 2.2 msec, inversion time [TI] = 180 msec, FA 50 degrees , matrix 128 x 256, 0.3 sec/slice) during the injection of Gadolinium-DTPA. Tissue concentration-time courses were deconvolved. Renal blood flow (RBF), volume of distribution (RVD), and mean transit time (MTT) were derived from the resulting impulse response function. RESULTS: Mean RBF, RVD, and MTT were 127 mL/min/100 mL (SD = 81 mL/min/100 mL), 40 mL/100 mL (SD 23 mL/100 mL), and 22 sec (SD = 9 sec). A significant moderately negative correlation was found between RBF and age (R = -0.447, P = 0.007), RVD and age (R = -0.420, P = 0.012). MTT and age did not show a significant correlation (R = 0.017, P = 0.924). Repeating this analysis for each gender revealed a moderate age dependence of RBF (R = -0.600 with P = 0.009) and RVD (R = -0.540 with P = 0.021) in the male group only. CONCLUSION: T1-DCE quantitative perfusion MRI was sufficiently sensitive to demonstrate a significant negative correlation of RBF and RVD with patient age. This was due to a moderate age dependence of these quantities in males that seems to be absent in females.

Histological findings compared with magnetic resonance and ultrasonographic imaging in irreversible postmastectomy lymphedema: a case study.

Postmastectomy edema is a current complication after axillary lymph node dissection in cases of breast cancer treatment. Staging is important in order to select those patients who can benefit from complex physical therapy (CPT). Different imaging techniques can be used to evaluate the edema. Ultrasonography (US) is a harmless, cheap, and easily applicable technique to visualize the dermal and subcutaneous tissue, but interpretation of the obtained images is not always evident. The aim of this study was to compare ultrasound images of irreversible edema with tissue histology, magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Ultrasonographic images of the edematous dermis show an homogeneous hypoechogenic dermal layer that appears on tissue histology to be less compact, due to the excess of fluid in the interstitium separating the collagen fibres and making it more transparent on light microscopy. MRI of the dermis gives a hyperintense signal, indicating the presence of fluid. In the subcutis, increase of the adipose tissue could be observed on US, MRI, and tissue histology. In the case of lymphedema, the area and perimeter of fat cells is significantly (p < 0.05) increased. Hypoechogenic areas near the muscle fascia are registered on US corresponding with epifascial fluid on MRI, and hyperechogenic branches are embedded within the adipose tissue, on tissue histology seen as large fibrotic septa enclosing adipose cells. MRI has a honeycomb picture corresponding with fluid bound to fibrosis.

Breast imaging. Preoperative breast cancer staging: comparison of USPIO-enhanced MR imaging and 18F-fluorodeoxyglucose (FDC) positron emission tomography (PET) imaging for axillary lymph node staging--initial findings.

Magnetic resonance (MR) imaging after ultra-small super paramagnetic iron oxide (USPIO) injection and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for preoperative axillary lymph node staging in patients with breast cancer were evaluated using histopathologic findings as the reference standard. USPIO-enhanced MR and FDG-PET were performed in ten patients with breast cancer who were scheduled for surgery and axillary node resection. T2-weighted fast spin echo, T1-weighted three-dimensional (3D) gradient echo, T2*-weighted gradient echo and gadolinium-enhanced T1-weighted 3D gradient echo with spectral fat saturation were evaluated. MR imaging before USPIO infusion was not performed. The results were correlated with FDG-PET (acquired with dedicated PET camera, visual analysis) and histological findings. The histopathologic axillary staging was negative for nodal malignancy in five patients and positive in the remaining five patients. There was one false positive finding for USPIO-enhanced MR and one false negative finding for FDG-PET. A sensitivity (true positive rate) of 100%, specificity (true negative rate) of 80%, positive predictive value of 80%, and negative predictive value of 100% were achieved for USPIO-enhanced MR and of 80%, 100%, 100%, 80% for FDG-PET, respectively. The most useful sequences in the detection of invaded lymph nodes were in the decreasing order: gadolinium-enhanced T1-weighted 3D gradient echo with fat saturation, T2*-weighted 2D gradient echo, T1-weighted 3D gradient echo and T2-weighted 2D spin echo. In our study, USPIO-enhanced T1 gradient echo after gadolinium injection and fat saturation emerged as a very useful sequence in the staging of lymph nodes. The combination of USPIO-enhanced MR and FDG-PET achieved 100% sensitivity, specificity, PPV and NPV. If these results are confirmed, the combination of USPIO MR with FDG-PET has the potential to identify the patient candidates for axillary dissection versus sentinel node lymphadenectomy.

Deconvolution of dynamic contrast-enhanced MRI data by linear inversion: choice of the regularization parameter.

Truncated singular value decomposition (TSVD) is an effective method for the deconvolution of dynamic contrast-enhanced MRI. Two robust methods for the selection of the truncation threshold on a pixel-by-pixel basis--generalized cross validation (GCV) and the L-curve criterion (LCC)--were optimized and compared to paradigms in the literature. The methods lead to improvements in the estimate of the residue function and of its maximum and converge properly with SNR. The oscillations typically observed in the solution vanish entirely and perfusion is more accurately estimated at small mean transit times. This results in improved image contrast and increased sensitivity to perfusion abnormalities, at the cost of 1-2 min in calculation time and isolated instabilities in the image. It is argued that the latter problem may be resolved by optimization. Simulated results for GCV and LCC are equivalent in terms of performance, but GCV is faster.

Imaging tutorial: differential diagnosis of bright lesions on diffusion-weighted MR images.

High sensitivity (94%) and specificity (100%) have been reported in the diagnosis of acute cerebral infarction with diffusion-weighted magnetic resonance (MR) imaging. However, high signal intensity on diffusion-weighted MR images and low apparent diffusion coefficient values (similar to the findings in acute cerebral infarction) were reported in such diverse conditions as hemorrhage, abscess, lymphoma, and even Creutzfeldt-Jakob disease. The differential diagnosis of these conditions (eg, acute ischemic infarction and acute cerebral hemorrhage) is critical for the determination of appropriate treatment. The authors present a systematic review of bright lesions on diffusion-weighted MR images and their differential diagnosis, with emphasis on the practical and clinical approaches of differential diagnosis.