No abstract

These findings enabled confirmation that MR spectroscopic imaging and DW imaging offer potential for in vivo noninvasive assessment of prostate cancer aggressiveness, and both modalities have comparable performance. The combination did not result in better performance. Nonetheless, the better performances of metabolite ratios in the TZ and of ADCs in the PZ suggest that they have complementary value.

No abstract

The purpose of this study was to investigate the effects on the brain of multiple sessions of blood–brain barrier (BBB) disruption using focused ultrasound (FUS) in combination with micro-bubbles over a range of acoustic exposure levels. Six weekly sessions of FUS, using acoustical pressures between 0.66 and 0.80 MPa, were performed under magnetic resonance guidance. The success and degree of BBB disruption was estimated by signal enhancement of post-contrast T1-weighted imaging of the treated area. Histopathological analysis was performed after the last treatment. The consequences of repeated BBB disruption varied from no indications of vascular damage to signs of micro-hemorrhages, macrophage infiltration, micro-scar formations and cystic cavities. The signal enhancement on the contrast-enhanced T1-weighted imaging had limited value for predicting small-vessel damage. T2-weighted imaging corresponded well with the effects on histopathology and could be used to study treatment effects over time. This study demonstrates that repeated BBB disruption by FUS can be performed with no or limited damage to the brain tissue.

In many studies, it has been demonstrated that (1)H MRSI of the human prostate has great potential to aid prostate cancer management, e.g. in the detection and localisation of cancer foci in the prostate or in the assessment of its aggressiveness. It is particularly powerful in combination with T2 -weighted MRI. Nevertheless, the technique is currently mainly used in a research setting. This review provides an overview of the state-of-the-art of three-dimensional MRSI, including the specific hardware required, dedicated data acquisition sequences and information on the spectral content with background on the MR-visible metabolites. In clinical practice, it is important that relevant MRSI results become available rapidly, reliably and in an easy digestible way. However, this functionality is currently not fully available for prostate MRSI, which is a major obstacle for routine use by inexperienced clinicians. Routine use requires more automation in the processing of raw data than is currently available. Therefore, we pay specific attention in this review on the status and prospects of the automated handling of prostate MRSI data, including quality control. The clinical potential of three-dimensional MRSI of the prostate is illustrated with literature examples on prostate cancer detection, its localisation in the prostate, its role in the assessment of cancer aggressiveness and in the selection and monitoring of therapy.

HER2-targeting antibodies (i.e. trastuzumab and pertuzumab) prolong survival in HER2-positive breast cancer patients with extracranial metastases. However, the response of brain metastases to these drugs is poor, and it is hypothesized that the blood-brain barrier (BBB) limits drug delivery to the brain. We investigated whether we could improve the response by temporary disruption of the BBB using focused ultrasound in combination with microbubbles. To study this, we inoculated 30 nude rats with HER2-positive cells derived from a brain metastasis of a breast cancer patient (MDA-MB-361). The animals were divided into three groups: a control-group that received no treatment; an antibody-only group that received six weekly treatments of trastuzumab and pertuzumab; and an ultrasound+antibody group that received trastuzumab and pertuzumab in combination with six weekly sessions of BBB disruption using focused ultrasound. In two animals, the leakiness of the tumors before disruption was evaluated using contrast-enhanced T1-weighted magnetic resonance imaging and found that the tumors were not leaky. The same technique was used to evaluate the effectiveness of BBB disruption, which was successful in all sessions. The tumor in the control animals grew exponentially with a growth constant of 0.042±0.011 mm3/day. None of the antibody-only animals responded to the treatment and the growth constant was 0.033±0.009 mm3/day during the treatment period. Four of the ten animals in the ultrasound+antibody-group showed a response to the treatment with an average growth constant of 0.010±0.007 mm3/day, compared to a growth constant 0.043±0.013 mm3/day for the six non-responders. After the treatment period, the tumors in all groups grew at similar rates. As the tumors were not leaky before BBB disruption and there were no responders in the antibody-only group, these results show that at least in some cases disruption of the BBB is necessary for a response to the antibodies in these brain metastases. Interestingly, only some of the rats responded to the treatment. We did not observe a difference in tumor volume at the start of the treatment, nor in HER2 expression or in contrast-enhancement on MRI between the responders and non-responders to explain this. Better understanding of why certain animals respond is needed and will help in translating this technique to the clinic. In conclusion, we demonstrate that BBB disruption using focused ultrasound in combination with antibody therapy can inhibit growth of breast cancer brain metastasis.

Proton magnetic resonance spectroscopic imaging (H MRSI) enables non-invasive assessment of certain metabolites in the prostate gland. Several studies have demonstrated that this metabolic information, in combination with anatomical information from T2-weighted MR imaging significantly improves prostate cancer detection, localization and disease characterization. The technology of H MRSI is continuously evolving with improvements of hardware and acquisition methods. Recently,P and C MRSI of the prostate have regained new interest after a dormant period of decades. This review focuses on recent technical progress of in vivoH MRSI of the prostate, in particular those that enhance clinical applicability at 3T with respect to commonly used techniques to examine the prostate. These developments consist of higher magnetic field strengths, and better MR coils and acquisition techniques. Besides the improvements for H MRSI, the developments and opportunities forP and C MRSI for the prostate are reviewed. Finally, we briefly reviewC MRS of the prostate, in particular the new possibilities with hyperpolarized substrates.

Multiparametric MRI is a useful tool for the discrimination between low-grade and high-grade PCa and performs better than any individual functional parameter in both the PZ and TZ. The 25th percentile of ADC + WO25 offered the optimal combination in the PZ, and the choline over spermine + creatine ratio + WO25 offered the optimal combination in the TZ. The ADC parameter has no additional value for the assessment of PCa aggressiveness in the TZ.