Cryoplasty, a freezing therapy, is being used for the treatment of restenosis in peripheral arteries. In addition, cryo-preserved arteries are increasingly used in vascular grafts. While studies are being performed to establish the efficacy of such treatments, very little is known about the postcryosurgical or postcryo-preservation changes in mechanical properties of the arteries. Few studies have examined the effect of freezing in the absence of cryoprotective agents (CPAs), and the several studies done in the presence of CPAs have given mixed results. To examine this issue further, we froze pig femoral arteries in a controlled rate freezer, using an aluminum probe, both in the presence at (-80 degrees C to 1 degrees C/min) and absence (at -20 degrees C for 2 or 5 mins) of CPA and Fetal bovine serum (FBS). Following freezing, artery samples were subjected to uniaxial tensile testing. The weights of the tissue were measured before and after freezing. Our results suggest that freezing does have an effect on stress-strain properties, particularly in the low stress region corresponding to physiological conditions. The mechanisms of this change in mechanical properties may include the loss of smooth muscle cell viability, damage to extra cellular matrix (ECM), bulk redistribution of water, or changes in alignment caused by ice crystal growth. In the case of samples frozen in the absence of CPA or FBS, the results indicated a drastic reduction in weight of the tissue suggesting the importance of bulk water redistribution as one underlying mechanism. To further examine potential mechanisms, we subjected cryopreserved vessels to the same uniaxial tests. The extent of changes in mechanical properties and bulk water redistribution was greatly attenuated; reinforcing that water movement might play a role in the changes observed with freezing.

Applications involving freeze-thaw, such as cryoplasty or cryopreservation can significantly alter artery biomechanics including an increase in physiological elastic modulus. Since artery biomechanics plays a significant role in hemodynamics, it is important to understand the mechanisms underlying these changes to be able to help control the biomechanical outcome post-treatments. Understanding of these mechanisms requires investigation of the freeze-thaw effect on arterial components (collagen, smooth muscle cells or SMCs), as well as the components' contribution to the overall artery biomechanics. To do this, isolated fresh swine arteries were subjected to thermal (freeze-thaw to -20 degrees C for 2 min or hyperthermia to 43 degrees C for 2 h) and osmotic (0.1-0.2 M mannitol) treatments; these treatments preferentially altered either the collagen matrix (hydration/stability) or smooth muscle cells (SMCs), respectively. Tissue dehydration, thermal stability and SMC functional changes were assessed from bulk weight measurements, analyses of the thermal denaturation profiles using Fourier transform infrared (FTIR) spectroscopy and in vitro arterial contraction/relaxation responses to norepinephrine (NE) and acetylcholine (AC), respectively. Additionally, Second Harmonic Generation (SHG) microscopy was performed on fresh and frozen-thawed arteries to directly visualize the changes in collagen matrix following freeze-thaw. Finally, the overall artery biomechanics was studied by assessing responses to uniaxial tensile testing. Freeze-thaw of arteries caused: (a) tissue dehydration (15% weight reduction), (b) increase in thermal stability (approximately 6.4 degrees C increase in denaturation onset temperature), (c) altered matrix arrangement observed using SHG and d) complete SMC destruction. While hyperthermia treatment also caused complete SMC destruction, no tissue dehydration was observed. On the other hand, while 0.2 M mannitol treatment significantly increased the thermal stability (approximately 4.8 degrees C increase in denaturation onset), 0.1 M mannitol treatment did not result in any significant change. Both 0.1 and 0.2 M treatments caused no change in SMC function. Finally, freeze-thaw (506+/-159 kPa), hyperthermia (268+/-132 kPa) and 0.2 M mannitol (304+/-125 kPa) treatments all caused significant increase in the physiological elastic modulus (Eartery) compared to control (185+/-92 kPa) with the freeze-thaw resulting in the highest modulus. These studies suggest that changes in collagen matrix arrangement due to dehydration as well as SMC destruction occurring during freeze-thaw are important mechanisms of freeze-thaw induced biomechanical changes.

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Rationale: 68 Ga-labelled somatostatin analog PET/CT (SSA PET/CT) is now standard of care component in management of neuroendocrine tumors (NETs). However, treatment response for NETs is still performed with morphologic size measurements from other modalities, which can result in inaccurate disease burden. Functional tumor volume (FTV) acquired from SSA PET/CT has been suggested as a possible metric, but no validated measurement tool to measure FTV exists. We tested the precision of multiple FTV computational approaches compared to morphologic volume measurements to identify a candidate for incorporation into future FTV studies to assess tumor burden more completely and accurately. Methods: The clinical and imaging data of 327 NET patients was collected at MSKCC between December 2016 and April 2018. Patients were required to have SSA PET/CT and dedicated CT scans within 6 weeks. and were excluded if they had intervention between scans. When paired studies were evaluated, 150 correlating lesions demonstrated somatostatin analog. Lesions were excluded if they contained necrotic components or demonstrated a lobulated shape. This resulted in 94 lesions in twenty patients. The FTV for each lesion was evaluated with a hand-drawn assessment and three automated techniques -a 50% threshold from SUVmax, 42% threshold from SUVmax, and background-subtracted lesion histogram-based (BSL) method. These measurements were compared to volume calculated from morphologic volume measurements. Results:The FTV calculation methods demonstrated varying amount of correlation to morphologic volume measurements. FTV using threshold of 42% of SUVmax with 0.706 correlation, hand-drawn volume from PET imaging with 0.657 correlation, FTV using threshold of 50% of SUVmax with 0.645 correlation, and BSL method with 0.596 correlation. The Bland-Altman plots indicates that all FTV methods have positive mean difference compared to morphological volume, with FTV from threshold of 50% relative to SUVmax demonstrating the smallest mean difference. Conclusion: FTV determined with thresholding of SUVmax demonstrated the strongest correlation with traditional morphologic lesion volume assessment and the least bias. This method outperformed FTV calculated from hand drawn volume assessments with regards to accuracy. Automated FTV assessment based on a threshold shows promise to better determine extent of disease and make better prognostic assessments for patients with NETs.

Intra-CS cryo balloon ablation is safe and can potentially replace endocardial RF ablation targeting the AV junction and the CS muscular sleeve.