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Background: Gadolinium-based contrast agents can be used to identify the blood-brain barrier (BBB) opening after inducing a focused ultrasound (FUS) cavitation effect in the presence of microbubbles. However, the use of gadolinium may be limited for frequent routine monitoring of the BBB opening in clinical applications., Purpose: To use a gradient-echo sequence without contrast agent administration for monitoring of acoustic cavitation., Study Type: Animal and phantom prospective., Phantom/animal Model: Static and flowing gel phantoms; six normal adult male Sprague-Dawley rats., Field Strength/sequence: 3T, 7T; fast low-angle shot sequence., Assessment: Burst FUS with acoustic pressures = 1.5, 2.2, 2.8 MPa; pulse repetition frequencies = 1, 10,100 Hz; and duty cycles = 2%, 5%, 10% were transmitted to the chamber of a static phantom with microbubble concentrations = 10%, 1%, 0.1%. MR slice thicknesses = 3, 6, 8 mm were acquired. In flowing phantom experiments, 0.1%, 0.25%, 0.5%, 0.75%, and 1% microbubbles were infused and transmitted by burst FUS with an acoustic pressure = 0.4 and 1 MPa. In in vivo experiments, 0.25% microbubbles was infused and 0.8 MPa burst FUS was transmitted to targeted brain tissue beneath the superior sagittal sinus. The mean signal intensity (SI) was normalized using the mean SI from pre-FUS., Statistical Tests: Two-tailed Student's t-test. P < 0.05 was considered statistically significant., Results: In the static phantom, the time courses of normalized SI decreases to minimum SI levels of 70-80%. In the flowing phantom, substantial normalized SI of 160-230% was present with variant acoustic pressures and microbubble concentrations. Compared with in vivo control rats, the brain tissue of experimental rats with transmission of FUS pulses exhibited considerable decreases of normalized SI (P < 0.001) because of the cavitation-induced perturbation of flow., Data Conclusion: Observing gradient-echo SI changes can help monitor the targeted location of microbubble-enhanced FUS, which in turn assists the monitoring of the BBB opening., Level of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:311-318., (© 2019 International Society for Magnetic Resonance in Medicine.)

Background: This study evaluated the performance of histogram analysis in the time course of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for differentiating cancerous tissues from benign tissues in the prostate., Methods: We retrospectively analyzed the histograms of DCE-MRI of 30 patients. Histograms within regions of interest(ROI) in the peripheral zone (PZ) and transitional zone (TZ) were separately analyzed. The maximum difference wash-in slope (MWS) and delay phase slope (DPS) were defined for each voxel. Differences in histogram parameters, namely the mean, standard deviation (SD), the coefficient of variation (CV), kurtosis, skewness, interquartile range (IQR), percentile (P10, P25, P75, P90, and P90P10), Range, and modified full width at half-maximum (mFWHM) between cancerous and benign tissues were assessed., Results: In the TZ, CV for ROIs of 7.5 and 10mm was the only significantly different parameter of the MWS (P = 0.034 and P = 0.004, respectively), whereas many parameters of the DPS (mean, skewness, P10, P25, P50, P75 and P90) differed significantly (P = <0.001-0.016 and area under the curve [AUC] = 0.73-0.822). In the PZ, all parameters of the MWS exhibited significant differences, except kurtosis and skewness in the ROI of 7.5mm(P = <0.001-0.017 and AUC = 0.865-0.898). SD, IQR, mFWHM, P90P10 and Range were also significant differences in the DPS (P = 0.001-0.035)., Conclusion: The histogram analysis of DCE-MRI is a potentially useful approach for differentiating prostate cancer from normal tissues. Different histogram parameters of the MWS and DPS should be applied in the TZ and PZ., Competing Interests: The authors have declared that no competing interests exist.

The susceptibility differences at the gas-liquid interface of microbubbles (MBs) allow their use as an intravascular susceptibility contrast agent for in vivo MRI. However, the characteristics of MBs are very different from those of the standard gadolinium-diethylenetriaminepentaacetic acid (Gd-DPTA) contrast agent, including the size distribution and hemodynamic properties, which could influence MRI outcomes. Here, we investigate quantitatively the correlation between the relative cerebral blood volume (rCBV) derived from Gd-DTPA (rCBV(Gd)) and the MB-induced susceptibility effect (ΔR(2*MB)) by conventional dynamic susceptibility contrast MRI (DSC-MRI). Custom-made MBs had a mean diameter of 0.92 µm and were capable of inducing 4.68 ± 3.02% of the maximum signal change (MSC). The MB-associated ΔR(2*MB) was compared with rCBV(Gd) in 16 rats on 4.7-T MRI. We observed a significant effect of the time to peak (TTP) on the correlation between ΔR(2*MB) and rCBV(Gd), and also found a noticeable dependence between TTP and MSC. Our findings suggest that MBs with longer TTPs can be used for the estimation of rCBV by DSC-MRI, and emphasize the critical effect of TTP on MB-based contrast MRI., (Copyright © 2013 John Wiley & Sons, Ltd.)

Deuterium oxide (D2 O), which is commercially available and nonradioactive, was proposed as a perfusion tracer before the clinical usage of conventional gadolinium-based MRI contrast agents. However, the sensitivity of direct deuterium detection is the major challenge for its application. In this study, we propose a contrast-enhanced strategy to indirectly trace administered D2 O by monitoring the signal attenuation of (1) H MRI. Experiments on D2 O concentration phantoms and in vivo rat brains were conducted to prove the concept of the proposed contrast mechanism. An average maximum signal drop ratio of 5.25 ± 0.91% was detected on (1) H MR images of rat brains with 2 mL of D2 O administered per 100 g of body weight. As a diffusible tracer for perfusion, D2 O infusion is a practicable method for the assessment of tissue perfusion and has the potential to provide different information from gadolinium-based contrast agents, which have limited permeability for blood vessels. Furthermore, the observed negative relaxivities of D2 O reveal the (1) H-D exchange effect. Therefore, applications of perfusion MRI with D2 O as a contrast agent are worthy of further investigation., (Copyright © 2013 John Wiley & Sons, Ltd.)

Dynamic contrast-enhanced MRI (DCE MRI) has been used to study tumor response to treatment for many years. In this study, the modified full width at half-maximum (mFWHM), calculated from the wash-in slope histogram, is proposed as a parameter for the evaluation of changes in tumor heterogeneity which respond to radiotherapy. Twenty-five patients with brain tumors were evaluated and divided into the nonresponder group (n = 11) and the responder group (n = 14) according to the Response Evaluation Criteria in Solid Tumors (RECIST). All selected tumors were evaluated by mFWHM ratios of post- to pre-therapy (the ratio was defined as the therapeutic mFWHM ratio, TMR). The changes in kurtosis of the histograms and the averaged K(trans) within a tumor were also calculated for comparison. The receiver operating characteristic analysis and Kaplan-Meier curves were used to examine the diagnosis ability. The TMR values were significantly higher in nonresponders than in responders (p < 0.001). When compared with the other two parameters, the proposed method also demonstrated better sensitivity and specificity. When adopting the TMR for the estimation of prognosis after therapy, there was a significant difference between the population survival curves. In conclusion, the derived mFWHM reflects tumor heterogeneity, and the ability to depict patient survival probability from TMR corresponds well with that from RECIST. The results reveal that, in brain tumors, progression may be exhibited not only by tumor size, but also by tumor heterogeneity., (Copyright © 2012 John Wiley & Sons, Ltd.)