This paper reports the development of an MRI-Safe robot for direct (interventional) MRI-guided endorectal prostate biopsy. The robot is constructed of nonmagnetic and electrically nonconductive materials, and is electricity free, using pneumatic actuation and optical sensors. Targeting biopsy lesions of MRI abnormality presents substantial clinical potential for the management of prostate cancer. The paper describes MRI-Safe requirements, presents the kinematic architecture, design and construction of the robot, and a comprehensive set of preclinical tests for MRI compatibility and needle targeting accuracy. The robot has a compact and simple 3 degree-of-freedom (DoF) structure, two for orienting a needle-guide and one to preset the depth of needle insertion. The actual insertion is performed manually through the guide and up to the preset depth. To reduce the complexity and size of the robot next to the patient, the depth setting DoF is remote. Experimental results show that the robot is safe to use in any MRI environment (MRI-Safe). Comprehensive MRI tests show that the presence and motion of the robot in the MRI scanner cause virtually no image deterioration or signal to noise ratio (SNR) change. Robot’s accuracy in bench test, CT-guided in-vitro, MRI-guided in-vitro and animal tests are 0.37mm, 1.10mm, 2.09mm, and 2.58mm respectively. These values are acceptable for clinical use.

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Iatrogenic injury to the healthy ureter during ureteroscope-guided ablation of malignant or nonmalignant disease can result in ureteral stricture. Transforming growth factor (TGF)-β1-mediated scar formation is considered to underlie ureteral stricture, but the cellular sources of this cytokine and the sequelae preceding iatrogenic stricture formation are unknown. Using a swine model of ureteral injury with irreversible electroporation (IRE), we evaluated the cellular sources of TGF-β1 and scar formation at the site of injury and examined in vitro whether the effects of TGF-β1 could be attenuated by pirfenidone. We observed that proliferation and α-smooth muscle actin expression by fibroblasts were restricted to injured tissue and coincided with proliferation of macrophages. Collagen deposition and scarring of the ureter were associated with increased TGF-β1 expression in both fibroblasts and macrophages. Using in vitro experiments, we demonstrated that macrophages stimulated by cells that were killed with IRE, but not LPS, secreted TGF-β1, consistent with a wound healing phenotype. Furthermore, using 3T3 fibroblasts, we demonstrated that stimulation with paracrine TGF-β1 is necessary and sufficient to promote differentiation of fibroblasts and increase collagen secretion. In vitro, we also showed that treatment with pirfenidone, which modulates TGF-β1 activity, limits proliferation and TGF-β1 secretion in macrophages and scar formation-related activity by fibroblasts. In conclusion, we identified wound healing-related macrophages to be an important source of TGF-β1 in the injured ureter, which may be a paracrine source of TGF-β1 driving scar formation by fibroblasts, resulting in stricture formation.