The Role of Imaging in Peripheral Interventions.

Patient evaluation is critical to identify and quantitate patient's disease. Aside from the patient's history and physical examination, imaging can help confirm and determine the extent of disease. Imaging can aid in treatment planning once the decision to proceed to intervention has been made. This chapter will discuss the role of imaging before and after peripheral arterial interventions and how it may improve intervention outcomes. It will discuss the value of the arterial noninvasive examinations (ankle-brachial index, toe-brachial index, pulse volume recordings, and arterial duplex ultrasound), computed tomographic angiograms, magnetic resonance angiogram, and intravascular ultrasound.

Could ultrasound-guided cryoablation be used to manage "low-risk" DCIS?: a feasibility case report.

Management of ductal carcinoma in-situ (DCIS) is controversial as there is concern that the majority of diagnoses will never become life threatening such that a subset of patients may be overtreated with surgery. Active surveillance is an alternative proposed management strategy; however, we cannot accurately predict which DCIS will never progress to invasive disease potentially undertreating a large proportion of women. We present a case of a 58-year-old female with DCIS successfully treated with only ultrasound-guided cryoablation without resection. A follow-up needle biopsy of the ablation zone was benign and imaging follow-up has demonstrated no evidence of disease at 14-months. Cryoablation of DCIS is feasible with appropriate patient selection and warrants further investigation as an alternative to surgical resection or active surveillance.

Targeting MMP-14 for dual PET and fluorescence imaging of glioma in preclinical models.

PURPOSE: There is a clinical need for agents that target glioma cells for non-invasive and intraoperative imaging to guide therapeutic intervention and improve the prognosis of glioma. Matrix metalloproteinase (MMP)-14 is overexpressed in glioma with negligible expression in normal brain, presenting MMP-14 as an attractive biomarker for imaging glioma. In this study, we designed a peptide probe containing a near-infrared fluorescence (NIRF) dye/quencher pair, a positron emission tomography (PET) radionuclide, and a moiety with high affinity to MMP-14. This novel substrate-binding peptide allows dual modality imaging of glioma only after cleavage by MMP-14 to activate the quenched NIRF signal, enhancing probe specificity and imaging contrast. METHODS: MMP-14 expression and activity in human glioma tissues and cells were measured in vitro by immunofluorescence and gel zymography. Cleavage of the novel substrate and substrate-binding peptides by glioma cells in vitro and glioma xenograft tumors in vivo was determined by NIRF imaging. Biodistribution of the radiolabeled MMP-14-binding peptide or substrate-binding peptide was determined in mice bearing orthotopic patient-derived xenograft (PDX) glioma tumors by PET imaging. RESULTS: Glioma cells with MMP-14 activity showed activation and retention of NIRF signal from the cleaved peptides. Resected mouse brains with PDX glioma tumors showed tumor-to-background NIRF ratios of 7.6-11.1 at 4 h after i.v. injection of the peptides. PET/CT images showed localization of activity in orthotopic PDX tumors after i.v. injection of 68Ga-binding peptide or 64Cu-substrate-binding peptide; uptake of the radiolabeled peptides in tumors was significantly reduced (p < 0.05) by blocking with the non-labeled-binding peptide. PET and NIRF signals correlated linearly in the orthotopic PDX tumors. Immunohistochemistry showed co-localization of MMP-14 expression and NIRF signal in the resected tumors. CONCLUSIONS: The novel MMP-14 substrate-binding peptide enabled PET/NIRF imaging of glioma models in mice, warranting future image-guided resection studies with the probe in preclinical glioma models.

Fluorescence Imaging of Nerves During Surgery.

OBJECTIVE: This review details the agents for fluorescence-guided nerve imaging in both preclinical and clinical use to identify factors important in selecting nerve-specific fluorescent agents for surgical procedures. BACKGROUND: Iatrogenic nerve injury remains a significant cause of morbidity in patients undergoing surgical procedures. Current real-time identification of nerves during surgery involves neurophysiologic nerve stimulation, which has practical limitations. Intraoperative fluorescence-guided imaging provides a complimentary means of differentiating tissue types and pathology. Recent advances in fluorescence-guided nerve imaging have shown promise, but the ideal agent remains elusive. METHODS: In February 2018, PubMed was searched for articles investigating peripheral nerve fluorescence. Key terms used in this search include: "intraoperative, nerve, fluorescence, peripheral nerve, visualization, near infrared, and myelin." Limits were set to exclude articles exclusively dealing with central nervous system targets or written in languages other than English. References were cross-checked for articles not otherwise identified. RESULTS: Of the nonspecific agents, tracers that rely on axonal transport showed the greatest tissue specificity; however, neurovascular dyes already enjoy wide clinical use. Fluorophores specific to nerve moieties result in excellent nerve to background ratios. Although noteworthy findings on tissue specificity, toxicity, and route of administration specific to each fluorescent agent were reported, significant data objectively quantifying nerve-specific fluorescence and toxicity are lacking. CONCLUSIONS: Fluorescence-based nerve enhancement has advanced rapidly over the past 10 years with potential for continued utilization and progression in translational research. An ideal agent would be easily administered perioperatively, would not cross the blood-brain barrier, and would fluoresce in the near-infrared spectrum. Agents administered systemically that target nerve-specific moieties have shown the greatest promise. Based on the heterogeneity of published studies and methods for reporting outcomes, it appears that the development of an optimal nerve imaging agent remains challenging.

Submucosal gland mucus strand velocity is decreased in chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) may be initiated by innately impaired host defense mechanisms that predispose the upper airways to infection. Recent evidence suggests tethering of submucosal gland mucus strands represents an inciting event within cystic fibrosis (CF) airways, occurring prior to onset of chronic infection. Submucosal gland hypertrophy and defective mucociliary clearance (MCC) are present in actively inflamed sinuses, but mucus strand velocity may also be affected as a secondary event, further contributing to chronic disease. The objective of this study is to assess whether mucus strand velocity is decreased in patients with CRS. METHODS: Mucosal explants from patients with and without CRS were submerged in Ringer's solution mixed with fluorescent nanospheres. Methacholine was then added, and videos demonstrating strand growth and detachment were generated from a time-lapse of Z-stack images using a multiphoton confocal microscope. Dynamic mucus strands were identified and individual velocities quantified with the MTrackJ plug-in of ImageJ. RESULTS: Fifteen patients met criteria for ex vivo analysis of mucus strand velocities (CRS, n = 9 vs controls, n = 6). Mucus strands were recorded (pixels/second) streaming from the submucosal gland openings. Average mucus strand velocities were significantly decreased in patients with CRS (1.53 ± 0.67 vs controls, 4.86 ± 1.68 pixels/second; p < 0.001). CONCLUSION: This study is the first to report evidence of abnormal mucus strand velocity from submucosal glands in diseased sinonasal mucosa. Future pharmacologic studies targeting this critical component of MCC are warranted.

Maintaining the Fire but Avoiding Burnout: Implementation and Evaluation of a Resident Well-Being Program.

BACKGROUND: There have been few programs designed to improve surgical resident well-being, and such efforts often lack formal evaluation. STUDY DESIGN: General surgery residents participated in the Energy Leadership Well-Being and Resiliency Program. They were assessed at baseline and 1 year after implementation using the Energy Leadership Index (measures emotional intelligence), Maslach Burnout Inventory General Survey, Perceived Stress Scale, the Beck Depression Inventory, and the annual required ACGME resident survey. Scores before and after implementation were compared using paired t-tests for continuous variables and chi-square tests for categorical variables. RESULTS: Forty-nine general surgery residents participate in the program. One year after implementation, resident score on the Energy Leadership Index improved (from 3.16 ± 0.24 to 3.24 ± 0.32; p = 0.03). Resident perceived stress decreased from baseline (Perceived Stress Scale score, from 17.0 ± 7.2 to 15.7 ± 6.2; p = 0.05). Scores on the emotional exhaustion scale of the Maslach Burnout Inventory decreased (from 16.8 ± 8.4 to 14.4 ± 8.5; p = 0.04). Resident-reported satisfaction improved in many areas; satisfaction with leadership skills, work relationships, communication skills, productivity, time management, personal freedom, and work-life balance, increased during the 1-year intervention (p = NS). On the annual ACGME resident survey, residents' evaluation of the program as positive or very positive increased from 80% to 96%. CONCLUSIONS: This study demonstrates that formal implementation of a program to improve resident well-being positively impacted residents' perceived stress, emotional exhaustion, emotional intelligence, life satisfaction, and their perception of the residency program. Formal evaluation and reporting of such efforts allow for reproducibility and scalability, with the potential for widespread impact on resident well-being.