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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. [ABSTRACT FROM AUTHOR]

Deuterium oxide (D2O), 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 D2O by monitoring the signal attenuation of 1H MRI. Experiments on D2O 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 1H MR images of rat brains with 2 mL of D2O administered per 100 g of body weight. As a diffusible tracer for perfusion, D2O 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 D2O reveal the 1H-D exchange effect. Therefore, applications of perfusion MRI with D2O as a contrast agent are worthy of further investigation. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

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 Ktrans 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. [ABSTRACT FROM AUTHOR]

Antiangiogenic therapy is widely administered in many cancers, and the antiangiogenic drug sorafenib offers moderate benefits in advanced hepatocellular carcinoma (HCC). However, antiangiogenic therapy can also lead to hypoxia-driven angiogenesis and immunosuppression in the tumor microenvironment (TME) and metastasis. Here, we report the synthesis and evaluation of NanoMnSor, a tumor-targeted, nanoparticle drug carrier that efficiently codelivers oxygen-generating MnO 2 and sorafenib into HCC. We found that MnO 2 not only alleviates hypoxia by catalyzing the decomposition of H 2 O 2 to oxygen but also enhances pH/redox-responsive T1-weighted magnetic resonance imaging and drug-release properties upon decomposition into Mn 2+ ions in the TME. Moreover, macrophages exposed to MnO 2 displayed increased mRNA associated with the immunostimulatory M1 phenotype. We further show that NanoMnSor treatment leads to sorafenib-induced decrease in tumor vascularization and significantly suppresses primary tumor growth and distal metastasis, resulting in improved overall survival in a mouse orthotopic HCC model. Furthermore, NanoMnSor reprograms the immunosuppressive TME by reducing the hypoxia-induced tumor infiltration of tumor-associated macrophages, promoting macrophage polarization toward the immunostimulatory M1 phenotype, and increasing the number of CD8 + cytotoxic T cells in tumors, thereby augmenting the efficacy of anti-PD-1 antibody and whole-cell cancer vaccine immunotherapies. Our study demonstrates the potential of oxygen-generating nanoparticles to deliver antiangiogenic agents, efficiently modulate the hypoxic TME, and overcome hypoxia-driven drug resistance, thereby providing therapeutic benefit in cancer.

Objective: This study investigates the application of a modified reversed gradient algorithm to the Propeller-EPI imaging method (periodically rotated overlapping parallel lines with enhanced reconstruction based on echo-planar imaging readout) for corrections of geometric distortions due to the EPI readout., Materials and Methods: Propeller-EPI acquisition was executed with 360-degree rotational coverage of the k-space, from which the image pairs with opposite phase-encoding gradient polarities were extracted for reversed gradient geometric and intensity corrections. The spatial displacements obtained on a pixel-by-pixel basis were fitted using a two-dimensional polynomial followed by low-pass filtering to assure correction reliability in low-signal regions. Single-shot EPI images were obtained on a phantom, whereas high spatial resolution T2-weighted and diffusion tensor Propeller-EPI data were acquired in vivo from healthy subjects at 3.0 Tesla, to demonstrate the effectiveness of the proposed algorithm., Results: Phantom images show success of the smoothed displacement map concept in providing improvements of the geometric corrections at low-signal regions. Human brain images demonstrate prominently superior reconstruction quality of Propeller-EPI images with modified reversed gradient corrections as compared with those obtained without corrections, as evidenced from verification against the distortion-free fast spin-echo images at the same level., Conclusions: The modified reversed gradient method is an effective approach to obtain high-resolution Propeller-EPI images with substantially reduced artifacts.