Abstract

BackgroundMouse models for treatment of late-stage prostate cancer are valuable tools, but assessing the extent of growth of the prostate and particularly its regression due to therapeutic intervention or castration is difficult due to the location, small size and interdigitated anatomy of the prostate gland in situ. Temporal monitoring of mouse prostate regression requires multiple animals and examination of histological sections.MethodsInitially, T2-weighted magnetic resonance imaging (MRI) was performed on normal year-old C57/BL6 mice. Individual mice were repeatedly imaged using inhalation anesthesia to establish the reproducibility of the method and to follow hormone manipulation of the prostate volume. Subsequently, MRI fat signal was suppressed using a chemical shift-selective (CHESS) pulse to avoid signal contamination and enhance discrimination of the prostate.ResultsHigh field (7T) MRI provides high resolution (117 × 117 μm in plane), highly reproducible images of the normal mouse prostate. Despite long imaging times, animals can be imaged repeatedly to establish reliability of volume measurements. Prostate volume declines following castration and subsequently returns to normal with androgen administration in the same animal. CHESS imaging allowed discrimination of both the margins of the prostate and the dorsal-lateral lobes of the prostate (DLP) from the ventral lobes (VP). Castration results in a 40% reduction in the volume of the DLP and a 75% reduction in the volume of the VP.ConclusionMRI assessment of the volume of the mouse prostate is precise and reproducible. MRI improves volumetric determination of the extent of regression and monitoring of the same mouse over time during the course of treatment is possible. Since assessing groups of animals at each time point is avoided, this improves the accuracy of the measurement of any manipulation effect and reduces the number of animals required.

Highlights

  • Mouse models for treatment of late-stage prostate cancer are valuable tools, but assessing the extent of growth of the prostate and its regression due to therapeutic intervention or castration is difficult due to the location, small size and interdigitated anatomy of the prostate gland in situ

  • The balance between mitosis and apoptosis is disrupted, and the prostate undergoes a wave of cell death, involuting the gland [3]

  • Imaging of the normal prostate Prostate volumes were measured in mature mice

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Summary

Methods

T2-weighted magnetic resonance imaging (MRI) was performed on normal yearold C57/BL6 mice. Individual mice were repeatedly imaged using inhalation anesthesia to establish the reproducibility of the method and to follow hormone manipulation of the prostate volume. MRI fat signal was suppressed using a chemical shift-selective (CHESS) pulse to avoid signal contamination and enhance discrimination of the prostate. Mice were housed individually in the UCI animal facility and all procedures were in accordance with institutional guidelines. Animals were anesthetized with Xylazine (13 mg/kg) and Ketamine (87 mg/kg), and castrated via scrotal incision. The incision was closed with surgical silk rather than wound clips for compatibility with MRI. There was neither weight gain nor loss greater than 10% for any animal during these manipulations. Mice were anesthetized as above, and positioned inside the instrument. Anesthesia was maintained using 1% isoflurane, 99% oxygen delivered via a nose cone for the duration of the imaging

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