Castration Levels of Testosterone Results in Atrophy of Androgen-Sensitive Perineal Muscles: A Potential Biomarker for Male Hypogonadism.

OBJECTIVES: To evaluate MRI-based measurements of androgen-sensitive perineal/pelvic muscles in men with prostate cancer before and after androgen deprivation therapy (ADT) as a novel imaging marker for end-organ effects of hypogonadism. Diagnosing hypogonadism or testosterone deficiency (TD) requires both low serum testosterone and clinical symptoms, such as erectile dysfunction and reduced libido. However, the non-specific nature of many TD symptoms makes it challenging to initiate therapy. Objective markers of TD help to better identify patients who may benefit from testosterone supplementation; however, current markers, such as low bone mineral density, lack sensitivity. Previous studies suggest that decreased bulbocavernosus-muscle (BCM) thickness may be associated with TD, although it remains unclear if this is a correlative relationship. METHODS: Data was prospectively collected for patients with intermediate/high-risk localized prostate cancer enrolled in a phase II trial (NCT02430480). Patients received ADT before prostatectomy and underwent prostate MRI pre-/post-ADT. BCM, ischiocavernosus-muscle (ICM), and levator-ani-muscle (LAM) measurements were made using T2W-MRI. Paired t-tests evaluated changes in BCM/ICM/LAM width, and linear regression analyses evaluated relationships between changes in testosterone and muscle width. RESULTS: Thirty-eight consecutive patients with pre-/post-ADT MRIs were analyzed. Baseline testosterone was 286.5ng/dl, and 36/38 patients had post-ADT testosterone <50ng/dL. Pre-ADT and post-ADT measurements of the bilateral BCM/ICM/LAM width were 7.16mm/7.95mm/5.53mm and 5.68mm/6.71mm/4.89mm, respectively (p<0.001). Decreases in testosterone predicted reduction in combined perineal muscle (BCM+ICM) width (p=0.032). CONCLUSIONS: Androgen deprivation led to significant and relatively rapid decreases in BCM/ICM/LAM thickness. This objective biomarker of low testosterone states may help identify patients who will potentially benefit from testosterone replacement.

A Novel Magnetic Resonance Imaging/Ultrasound Fusion Prostate Biopsy Technique Using Transperineal Ultrasound: An Initial Experience.

OBJECTIVE: To report an initial experience with a novel, "fully" transperineal (TP) prostate fusion biopsy using an unconstrained ultrasound transducer placed on the perineal skin to guide biopsy needles inserted via a TP approach. METHODS: Conventional TP prostate biopsies for detection of prostate cancer have been performed with transrectal ultrasound, requiring specialized hardware, imposing limitations on needle trajectory, and contributing to patient discomfort. Seventy-six patients with known or suspected prostate cancer underwent 78 TP biopsy sessions in an academic center between June 2018 and April 2022 and were included in this study. These patients underwent TP prostate fusion biopsy using a grid or freehand device with transrectal ultrasound as well as TP prostate fusion biopsy using TP ultrasound in the same session. Per-session and per-lesion cancer detection rates were compared for conventional and fully TP biopsies using Fisher exact and McNemar's tests. RESULTS: After a refinement period in 30 patients, 92 MRI-visible prostate lesions were sampled in 46 subsequent patients, along with repeat biopsies in 2 of the 30 patients from the refinement period. Grade group ≥2 cancer was diagnosed in 24/92 lesions (26%) on conventional TP biopsy (17 lesions with grid, 7 with freehand device), and in 25/92 lesions (27%) on fully TP biopsy (P = 1.00), with a 73/92 (79%) rate of agreement for grade group ≥2 cancer between the two methods. CONCLUSION: Fully TP biopsy is feasible and may detect prostate cancer with detection rates comparable to conventional TP biopsy.

Expanding the Types of Lipids Amenable to Native Mass Spectrometry of Lipoprotein Complexes.

Native mass spectrometry (MS) has become an important tool for the analysis of membrane proteins. Although detergent micelles are the most commonly used method for solubilizing membrane proteins for native MS, nanoscale lipoprotein complexes such as nanodiscs are emerging as a promising complementary approach because they solubilize membrane proteins in a lipid bilayer environment. However, prior native MS studies of intact nanodiscs have employed only a limited set of phospholipids that are similar in mass. Here, we extend the range of lipids that are amenable to native MS of nanodiscs by combining lipids with masses that are simple integer multiples of each other. Although these lipid combinations create complex distributions, overlap between resonant peak series allows interpretation of nanodisc spectra containing glycolipids, sterols, and cardiolipin. We also investigate the gas-phase stability of nanodiscs with these new lipids towards collisional activation. We observe that negative ionization mode or charge reduction stabilizes nanodiscs and is essential to preserving labile lipids such as sterols. These new approaches to native MS of nanodiscs will enable future studies of membrane proteins embedded in model membranes that more accurately mimic natural bilayers. Graphical Abstract.