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An abstract of the article "Dosimetry Characterization of a Multi-Beam Radiotherapy Treatment for Age-Related Macular Degeneration," by C. Lee, M. Gertner, E. Chell, S. Hansen and W. Bolch is presented.

Background MRI-guided focal therapy (FT) allows for accurate targeting of localized clinically significant prostate cancer (csPCa) while preserving healthy prostate tissue, but the long-term outcomes of this approach require more study. Purpose To assess the 2-year oncological and functional outcomes of men with intermediate-risk prostate cancer (PCa) treated with targeted FT. Materials and Methods In this single-center prospective phase II trial, men with localized unifocal intermediate-risk PCa underwent transrectal MRI-guided focused ultrasound between July 2016 and July 2019. Planned ablation volumes included 10-mm margins when possible. Data regarding adverse events were collected and quality-of-life questionnaires were completed by participants at 6 weeks and at 5, 12, 18, and 24 months after treatment. Multiparametric MRI and targeted and systematic biopsies were performed at 24 months. Ablation volumes were determined by manual contouring of nonperfused volumes on immediate contrast-enhanced images. Generalized estimating equations were used to model trends in quality-of-life measures. Results Treatment was successfully completed in the 44 participants (median age, 67 years; IQR, 62-70 years; 36 patients with grade group [GG] 2; eight patients with GG 3). No major adverse events from treatment were recorded. One participant refused biopsy at 24 months. After 2 years, 39 of 43 participants (91%) had no csPCa at the treatment site and 36 of 43 (84%) had no cancer in the entire gland. No changes in International Index of Erectile Function-15 score or International Prostate Symptom Score were observed during 2-year follow-up ( P = .73 and .39, respectively). Conclusion The majority of men treated with MRI-guided focused ultrasound for intermediate risk PCa had negative results for csPCa at biopsy 2 years after treatment. Additionally, there was no significant decline in quality of life per the validated questionnaires. Clinical trial registration no. NCT02968784 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Woodrum in this issue.

Objective: Determine the multiparametric magnetic resonance imaging (mpMRI) appearance of the prostate following focal laser ablation (FLA) for PCa and to identify imaging characteristics associated with recurrent disease., Methods: Retrospective analysis of patients who underwent FLA for low-intermediate risk PCa between 2010 and 2014 was performed. Early (median 4 months) and late mpMRI (median 49 months) follow-up were qualitatively assessed for T 2 -weighted, dynamic contrast enhanced (DCE) and diffusion weighted imaging (DWI) appearances and also compared to corresponding PSA values and biopsy results., Results: 55 cancers were treated in 54 men (mean age 61.0 years). Early mpMRI was performed in 30 (54.5%) patients while late follow-up mpMRI in 42 (84%). Ill-defined scarring with and without atrophy at the treatment site were the most common appearances. In patients with paired MRI and biopsy, one of four patients with clinically significant PCa on biopsy (≥GG2 or≥6 mm GG1) showed hyperenhancement or restricted diffusion at early follow-up. At late follow-up, positive biopsies were seen in 5/8 (63%) cases with hyperenhancement and 5/6 (83%) cases with restricted diffusion at the treatment site. PSA change was not associated with biopsy results at either time point., Conclusion: mpMRI is able to document the morphological and temporal changes following focal therapy. It has limited ability to detect recurrent disease in early months following treatment. Late-term mpMRI is sensitive at identifying patients with recurrent disease. Small sample size is, however, a limitation of the study., Advances in Knowledge: Implementing MRI in follow-up after FT may be useful in predicting residual or recurrent PCa and therefore provide reliable outcome data.

While focal therapy (FT) is increasingly endorsed for treating localized prostate cancer in the appropriately selected patient, management of recurrences following FT is not well-established in the literature. This case series describes three patients who received high-intensity focal ultrasound (HIFU) for primary treatment followed by focal laser interstitial thermal therapy (FLTT) for salvage therapy treated in the context of an ongoing clinical trial. Evaluation of these reported patients demonstrates that FLTT is feasible in the salvage setting with promising short-term oncologic outcomes and with the potential to preserve functional outcomes. Repeat focal therapy for previous failures is feasible however, it requires sophisticated imaging modalities for the accurate identification of recurrence and treatment of the tumor., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Over the past four decades, there have been progressive changes in the epidemiology of traumatic spinal cord injury (tSCI). We assessed trends in demographic and injury-related variables in traumatic cervical spinal cord injury (tCSCI) patients over an 18-year period at a single Level I trauma center. We included all magnetic resonance imaging-confirmed tCSCI patients ≥15 years of age for years 2001-2018. Among 1420 patients, 78.3% were male with a mean age 51.5 years. Etiology included falls (46.9%), motor vehicle collisions (MVCs; 34.2%), and sports injuries (10.9%). Median American Spinal Injury Association (ASIA) Motor Score (AMS) was 44, complete tCSCI was noted in 29.6% of patients, fracture dislocations were noted in 44.7%, and median intramedullary lesion length (IMLL) was 30.8 mm (complete injuries 56.3 mm and incomplete injuries 27.4 mm). Over the study period, mean age and proportion of falls increased ( p  < 0.001) whereas proportion attributable to MVCs and sports injuries decreased ( p  < 0.001). Incomplete injuries, AMS, and the proportion of patients with no fracture dislocations increased whereas complete injuries decreased significantly. IMLL declined ( p  = 0.17) and proportion with hematomyelia did not change significantly. In adjusted regression models, increase in age and decreases in prevalence of MVC mechanism and complete injuries over time remained statistically significant. Changes in demographic and injury-related characteristics of tCSCI patients over time may help explain the observed improvement in outcomes. Further, improved clinical outcomes and drop in IMLL may reflect improvements in initial risk assessment and pre-hospital management, advances in healthcare delivery, and preventive measures including public education.

Purpose: To evaluate the efficacy and safety of iTEAR, a novel, portable, sonic external neuromodulation device, for the treatment of dry eye disease (DED)., Methods: This was a multicenter, open-label, single-arm clinical trial that included adult patients with DED with a Schirmer score of ≤10 mm in at least one eye. Enrolled subjects were instructed to apply the study device at least twice per day for 30 seconds bilaterally to the external nasal nerve. After the initial baseline visit, patients were followed up at days 3, 14, 30, 90, and 180. The primary efficacy endpoint was the Schirmer index (change from unstimulated to stimulated tear production as measured by the Schirmer test) at day 30. The major secondary endpoint was the change in symptoms of DED at day 30 evaluated using the Ocular Surface Disease Index (OSDI)., Results: A total of 101 subjects evaluated at day 30 had a mean Schirmer index of 9.4 mm (95% confidence interval [CI], 7.4-11.3), and the baseline OSDI improved by an average of 14.4 (95% CI, 11.1-17.7). Both endpoints were highly statistically and clinically significant at all time points. There were two mild unanticipated adverse events definitely related to the device., Conclusions: The safety and efficacy of the iTEAR device observed in this study support its indication for treating DED., Translational Relevance: Neurostimulation has the potential to improve signs and symptoms of DED., Competing Interests: Disclosure: M.H. Ji, None; D.M. Moshfeghi, None; L. Periman (C); D. Kading (C); C. Matossian, None; G. Walman, None; S. Markham, None; A. Mu, None; A. Jayaram, None; M. Gertner, Olympic Ophthalmics, Inc. (F, I); P. Karpecki (C); N.J. Friedman (C, I), (Copyright 2020 The Authors.)

Purpose: The aim of this study was to compare biopsy detection of intraductal and cribriform pattern invasive prostate carcinoma in multiparametric magnetic resonance imaging positive and negative regions of the prostate., Materials and Methods: We queried a prospectively maintained, single institution database to identify patients who underwent multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy and concurrent systematic sextant biopsy of magnetic resonance imaging negative regions between January 2013 and May 2016. All multiparametric magnetic resonance imaging targets were reviewed retrospectively by 2 readers for the PI-RADS™ (Prostate Imaging-Reporting and Data System), version 2 score, the maximum dimension, the apparent diffusion coefficient parameter and whether positive or negative on dynamic contrast enhancement sequence. Biopsy slides were reviewed by 2 urological pathologists for Gleason score/Grade Group and the presence or absence of an intraductal/cribriform pattern., Results: A total of 154 patients were included in study. Multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy and systematic sextant biopsy of magnetic resonance imaging negative regions were negative for prostate carcinoma in 51 patients, leaving 103 available for the correlation of multiparametric magnetic resonance imaging and the intraductal/cribriform pattern. Prostate carcinoma was identified by multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy in 93 cases and by systematic sextant biopsy of magnetic resonance imaging negative regions in 76 (p = 0.008). Intraductal/cribriform positive tumor was detected in 23 cases, including at the multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy site in 22 and at the systematic sextant biopsy of magnetic resonance imaging negative region site in 3 (p <0.001). The intraductal/cribriform pattern was significantly associated with a PI-RADS score of 5 and a decreasing apparent diffusion coefficient value (p = 0.008 and 0.005, respectively). In 19 of the 23 cases with the intraductal/cribriform pattern prior 12-core standard systematic biopsy was negative in 8 and showed Grade Group 1 disease in 11., Conclusions: Multiparametric magnetic resonance imaging/ultrasound fusion targeted biopsy was associated with significantly increased detection of intraductal/cribriform positive prostate carcinoma compared to systematic sextant biopsy of multiparametric magnetic resonance imaging negative regions. This supports the role of magnetic resonance imaging to enhance the detection of clinically aggressive intraductal/cribriform positive prostate carcinoma., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this double-blind, randomized, sham-controlled study was to verify the blood pressure (BP)-lowering efficacy of externally delivered focused ultrasound for renal denervation (RDN)., Background: Nonrandomized, first proof-of-concept study and experimental evidence suggested that noninvasive techniques of RDN emerged as an alternative approach of RDN to invasive technologies., Methods: WAVE IV, an international, randomized (1 : 1) sham-controlled, double-blind prospective clinical study, was prematurely stopped. Patients were enrolled if office BP was at least 160 mmHg and 24-h ambulatory BP was at least 135 mmHg, while taking three or more antihypertensive medications. The treatment consisted of bilateral RDN using therapeutic levels of ultrasound energy and the sham consisted of bilateral application of diagnostic levels of ultrasound energy., Results: In the 81 treated patients neither changes in office BP at 12 and 24 weeks, nor changes in 24-h ambulatory BP at 24-week follow-up visit differed between the two groups significantly. Of note, no safety signal was observed. Adherence analysis disclosed full adherence in 77% at baseline and 82% at 6 months' follow-up visit. Post hoc analysis revealed that stricter criteria for stabilization of BP at baseline were associated with a numerically greater change in 24-h ambulatory BP in the RDN group than in the sham group., Conclusion: Our data did not prove that antihypertensive efficacy of the externally delivered focused ultrasound for RDN was greater than the sham effect. Stabilization of BP at baseline was identified as an important determinant of BP changes.

The mammalian target of rapamycin (mTOR) is a key regulator of cell growth, autophagy, translation, and survival. Dysregulation of mTOR signaling is associated with cancer, diabetes, and autism. However, a role for mTOR signaling in neuronal death is not well delineated. Here we show that global ischemia triggers a transient increase in mTOR phosphorylation at S2448, whereas decreasing p-mTOR and functional activity in selectively vulnerable hippocampal CA1 neurons. The decrease in mTOR coincides with an increase in biochemical markers of autophagy, pS317-ULK-1, pS14-Beclin-1, and LC3-II, a decrease in the cargo adaptor p62, and an increase in autophagic flux, a functional readout of autophagy. This is significant in that autophagy, a catabolic process downstream of mTORC1, promotes the formation of autophagosomes that capture and target cytoplasmic components to lysosomes. Inhibitors of the lysosomal (but not proteasomal) pathway rescued the ischemia-induced decrease in mTOR, consistent with degradation of mTOR via the autophagy/lysosomal pathway. Administration of the mTORC1 inhibitor rapamycin or acute knockdown of mTOR promotes autophagy and attenuates ischemia-induced neuronal death, indicating an inverse causal relation between mTOR, autophagy, and neuronal death. Our findings identify a novel and previously unappreciated mechanism by which mTOR self-regulates its own levels in hippocampal neurons in a clinically relevant model of ischemic stroke., Competing Interests: The authors declare no conflict of interest.