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Browsing by Author "Connors, Bret A."
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Item Comparison of Tissue Injury from Focused Ultrasonic Propulsion of Kidney Stones Versus Extracorporeal Shock Wave Lithotripsy(Elsevier, 2014-01) Connors, Bret A.; Evan, Andrew P.; Blomgren, Philip M.; Hsi, Ryan S.; Harper, Jonathan D.; Sorensen, Mathew D.; Wang, Yak-Nam; Simon, Julianna C.; Paun, Marla; Starr, Frank; Cunitz, Bryan W.; Bailey, Michael R.; Lingeman, James E.; Department of Anatomy & Cell Biology, IU School of MedicinePurpose Focused ultrasonic propulsion is a new non-invasive technique designed to move kidney stones and stone fragments out of the urinary collecting system. However, the extent of tissue injury associated with this technique is not known. As such, we quantitated the amount of tissue injury produced by focused ultrasonic propulsion under simulated clinical treatment conditions, and under conditions of higher power or continuous duty cycles, and compared those results to SWL injury. Materials and Methods A human calcium oxalate monohydrate stone and/or nickel beads were implanted (with ureteroscopy) into 3 kidneys of live pigs (45–55 kg) and repositioned using focused ultrasonic propulsion. Additional pig kidneys were exposed to SWL level pulse intensities or continuous ultrasound exposure of 10 minutes duration (ultrasound probe either transcutaneous or on the kidney). These kidneys were compared to 6 kidneys treated with an unmodified Dornier HM3 Lithotripter (2400 shocks, 120 SWs/min and 24 kV). Histological analysis was performed to assess the volume of hemorrhagic tissue injury created by each technique (% functional renal volume, FRV). Results SWL produced a lesion of 1.56±0.45% FRV. Ultrasonic propulsion produced no detectable lesion with the simulated clinical treatment. A lesion of 0.46±0.37% FRV or 1.15±0.49% FRV could be produced if excessive treatment parameters were used while the ultrasound probe was placed on the kidney. Conclusions Focused ultrasonic propulsion produced no detectable morphological injury to the renal parenchyma when using clinical treatment parameters and produced injury comparable in size to SWL when using excessive treatment parameters.Item Development of a Novel Magnetic Resonance Imaging Acquisition and Analysis Workflow for the Quantification of Shock Wave Lithotripsy-Induced Renal Hemorrhagic Injury(Springer, 2017-10) Handa, Rajash K.; Territo, Paul R.; Blomgren, Philip M.; Persohn, Scott A.; Lin, Chen; Johnson, Cynthia D.; Jiang, Lei; Connors, Bret A.; Hutchins, Gary D.; Anatomy and Cell Biology, School of MedicineIntroduction The current accepted standard for quantifying shock wave lithotripsy (SWL)-induced tissue damage is based on morphometric detection of renal hemorrhage in serial tissue sections from fixed kidneys. This methodology is time and labor intensive and is tissue destructive. We have developed a non-destructive magnetic resonance imaging (MRI) method that permits rapid assessment of SWL-induced hemorrhagic lesion volumes in post-mortem kidneys using native tissue contrast to reduce cycle time. Methods Kidneys of anesthetized pigs were targeted with shock waves using the Dornier Compact S lithotripter. Harvested kidneys were then prepared for tissue injury quantification. T1 weighted (T1W) and T2 weighted (T2W) images were acquired on a Siemens 3T Tim Trio MRI scanner. Images were co-registered, normalized, difference (T1W–T2W) images generated, and volumes classified and segmented using a Multi-Spectral Neural Network (MSNN) classifier. Kidneys were then subjected to standard morphometric analysis for measurement of lesion volumes. Results Classifications of T1W, T2W and difference image volumes were correlated with morphometric measurements of whole kidney and parenchymal lesion volumes. From these relationships, a mathematical model was developed that allowed predictions of the morphological parenchymal lesion volume from MRI whole kidney lesion volumes. Predictions and morphology were highly correlated (R=0.9691, n=20) and described by the relationship y=0.84x+0.09, and highly accurate with a sum of squares difference error of 0.79%. Conclusions MRI and the MSNN classifier provide a semi-automated segmentation approach, which provide a rapid and reliable means to quantify renal injury lesion volumes due to SWL.Item Effect of renal shock wave lithotripsy on the development of metabolic syndrome in a juvenile swine model: a pilot study(Elsevier, 2015-04) Handa, Rajash K.; Liu, Ziyue; Connors, Bret A.; Alloosh, Mouhamad; Basile, David P.; Tune, Johnathan D.; Sturek, Michael; Evan, Andrew P.; Lingeman, James E.; Department of Anatomy & Cell Biology, IU School of MedicinePURPOSE: We performed a pilot study to assess whether renal shock wave lithotripsy influences metabolic syndrome onset and severity. MATERIALS AND METHODS: Three-month-old juvenile female Ossabaw miniature pigs were treated with shock wave lithotripsy (2,000 shock waves at 24 kV with 120 shock waves per minute in 2) or sham shock wave lithotripsy (no shock waves in 2). Shock waves were targeted to the upper pole of the left kidney to model treatment that would also expose the pancreatic tail to shock waves. Pigs were then instrumented to directly measure arterial blood pressure via an implanted radiotelemetry device. They later received a hypercaloric atherogenic diet for about 7 months. Metabolic syndrome development was assessed by the intravenous glucose tolerance test. RESULTS: Metabolic syndrome progression and severity were similar in the sham treated and lithotripsy groups. The only exception arterial blood pressure, which remained relatively constant in sham treated pigs but began to increase at about 2 months towards hypertensive levels in lithotripsy treated pigs. Metabolic data on the 2 groups were pooled to provide a more complete assessment of metabolic syndrome development and progression in this juvenile pig model. The intravenous glucose tolerance test revealed substantial insulin resistance with impaired glucose tolerance within 2 months on the hypercaloric atherogenic diet with signs of further metabolic impairment at 7 months. CONCLUSIONS: These preliminary results suggest that renal shock wave lithotripsy is not a risk factor for worsening glucose tolerance or diabetes mellitus onset. However, it appears to be a risk factor for early onset hypertension in metabolic syndrome.Item Evaluation of an experimental electrohydraulic discharge device for extracorporeal shock wave lithotripsy: Pressure field of sparker array(Acoustical Society of America, 2017-11) Li, Guangyan; Connors, Bret A.; Schaefer, Ray B.; Gallagher, John J.; Evan, Andrew P.; Anatomy and Cell Biology, School of MedicineIn this paper, an extracorporeal shock wave source composed of small ellipsoidal sparker units is described. The sparker units were arranged in an array designed to produce a coherent shock wave of sufficient strength to fracture kidney stones. The objective of this paper was to measure the acoustical output of this array of 18 individual sparker units and compare this array to commercial lithotripters. Representative waveforms acquired with a fiber-optic probe hydrophone at the geometric focus of the sparker array indicated that the sparker array produces a shock wave (P+ ∼40-47 MPa, P- ∼2.5-5.0 MPa) similar to shock waves produced by a Dornier HM-3 or Dornier Compact S. The sparker array's pressure field map also appeared similar to the measurements from a HM-3 and Compact S. Compared to the HM-3, the electrohydraulic technology of the sparker array produced a more consistent SW pulse (shot-to-shot positive pressure value standard deviation of ±4.7 MPa vs ±3.3 MPa).Item Functional and Morphological Changes Associated with Burst Wave Lithotripsy-Treated Pig Kidneys(Mary Ann Liebert Inc., 2022-11-28) Connors, Bret A.; Gardner, Tony; Liu, Ziyue; Lingeman, James E.; Kreider, Wayne; Williams , James C.; Biostatistics and Health Data Science, School of MedicinePurpose: Burst wave lithotripsy (BWL) is a new technique for comminution of urinary stones. This technology is noninvasive, has a low positive pressure magnitude, and is thought to produce minor amounts of renal injury. However, little is known about the functional changes related to BWL treatment. In this study, we sought to determine if clinical BWL exposure produces a functional or morphological change in the kidney. Materials and Methods: Twelve female pigs were prepared for renal clearance assessment and served as either sham time controls (6) or were treated with BWL (6). In the treated group, 1 kidney in each pig was exposed to 18,000 pulses at 10 pulses/s with 20 cycles/pulse. Pressure levels related to each pulse were 12 and −7 MPa. Inulin (glomerular filtration rate, GFR) and para-aminohippuric acid (effective renal plasma flow, eRPF) clearance was measured before and 1 hour after treatment. Lesion size analysis was performed to assess the volume of hemorrhagic tissue injury created by each treatment (% FRV). Results: No visible gross hematuria was observed in any of the collected urine samples of the treated kidneys. BWL exposure also did not lead to a change in GFR or eRPF after treatment, nor did it cause a measurable amount of hemorrhage in the tissue. Conclusion: Using the clinical treatment parameters employed in this study, BWL did not cause an acute change in renal function or a hemorrhagic lesion.Item Intraluminal measurement of papillary duct urine pH, in vivo: a pilot study in the swine kidney(Springer, 2016-06) Handa, Rajash K.; Lingeman, James E.; Bledsoe, Sharon B.; Evan, Andrew P.; Connors, Bret A.; Johnson, Cynthia D.; Department of Anatomy and Cell Biology, School of MedicineWe describe the in vivo use of an optic-chemo microsensor to measure intraluminal papillary duct urine pH in a large mammal. Fiber-optic pH microsensors have a tip diameter of 140-µm that allows insertion into papillary Bellini ducts to measure tubule urine proton concentration. Anesthetized adult pigs underwent percutaneous nephrolithotomy to access the lower pole of the urinary collecting system. A flexible nephroscope was advanced towards an upper pole papilla with the fiber-optic microsensor contained within the working channel. The microsensor was then carefully inserted into Bellini ducts to measure tubule urine pH in real time. We successfully recorded tubule urine pH values in five papillary ducts from three pigs (1 farm pig and 2 metabolic syndrome Ossabaw pigs). Our results demonstrate that optical microsensor technology can be used to measure intraluminal urine pH in real time in a living large mammal. This opens the possibility for application of this optical pH sensing technology in nephrolithiasis.Item Mechanism by which shock wave lithotripsy can promote formation of human calcium phosphate stones(American Physiological Society, 2015-04-15) Evan, Andrew P.; Coe, Fredric L.; Connors, Bret A.; Handa, Rajash K.; Lingeman, James E.; Worcester, Elaine M.; Department of Anatomy & Cell Biology, IU School of MedicineHuman stone calcium phosphate (CaP) content correlates with higher urine CaP supersaturation (SS) and urine pH as well as with the number of shock wave lithotripsy (SWL) treatments. SWL does damage medullary collecting ducts and vasa recta, sites for urine pH regulation. We tested the hypothesis that SWL raises urine pH and therefore Cap SS, resulting in CaP nucleation and tubular plugging. The left kidney (T) of nine farm pigs was treated with SWL, and metabolic studies were performed using bilateral ureteral catheters for up to 70 days post-SWL. Some animals were given an NH4Cl load to sort out effects on urine pH of CD injury vs. increased HCO3 (-) delivery. Histopathological studies were performed at the end of the functional studies. The mean pH of the T kidneys exceeded that of the control (C) kidneys by 0.18 units in 14 experiments on 9 pigs. Increased HCO3 (-) delivery to CD is at least partly responsible for the pH difference because NH4Cl acidosis abolished it. The T kidneys excreted more Na, K, HCO3 (-), water, Ca, Mg, and Cl than C kidneys. A single nephron site that could produce losses of all of these is the thick ascending limb. Extensive injury was noted in medullary thick ascending limbs and collecting ducts. Linear bands showing nephron loss and fibrosis were found in the cortex and extended into the medulla. Thus SWL produces tubule cell injury easily observed histopathologically that leads to functional disturbances across a wide range of electrolyte metabolism including higher than control urine pH.Item Percutaneous Renal Access: Surgical Factors Involved in the Acute Reduction of Renal Function(Mary Ann Liebert, Inc., 2016-02) Handa, Rajash K.; Johnson, Cynthia D.; Connors, Bret A.; Evan, Andrew P.; Lingeman, James E.; Liu, Ziyue; Department of Anatomy & Cell Biology, IU School of MedicineINTRODUCTION AND OBJECTIVE: Studies in patients and experimental animals have shown that percutaneous nephrolithotomy (PCNL) can acutely impair glomerular filtration and renal perfusion, but the factors contributing to this decline in renal function are unknown. The present study assessed the contribution of needle puncture of the kidney vs dilation of the needle tract to the acute decline in renal hemodynamic and tubular transport function associated with PCNL surgery. MATERIALS AND METHODS: Acute experiments were performed in three groups of anesthetized adult farm pigs: sham-percutaneous access (PERC), that is, no surgical procedure (n = 7); a single-needle stick to access the renal collecting system (n = 8); expansion of the single-needle access tract with a 30F NephroMax balloon dilator and insertion of a nephrostomy sheath (n = 10). The glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and renal extraction of para-amino hippurate (EPAH, estimates tubular organic anion transporter [OAT] activity) were assessed before and 1 to 4.5 hours after sham-PERC or PERC surgical procedures. RESULTS: Overall, GFR responses were similar in all three groups. Sham-treated PERC pigs showed no significant change in ERPF over the experimental observation period, whereas a single-needle stick to access the renal collecting system resulted in renal vasoconstriction (∼30% reduction in ERPF, p < 0.05). Dilation of the single-needle access tract to create the nephrostomy did not lead to a further decline in ERPF. PERC surgical procedure-mediated renal vasoconstriction was most evident at the 1-hour posttreatment time point. A reduction in EPAH was only observed in pig kidneys with a nephrostomy. CONCLUSIONS: Needle puncture of the kidney for percutaneous access to the renal collecting system is the major driving force for the renal vasoconstriction observed after PCNL surgery, whereas creation of the nephrostomy appears to be largely responsible for decreasing tubular OAT activity.Item Preliminary Report on Stone Breakage and Lesion Size Produced by a New Extracorporeal Electrohydraulic (Sparker Array) Discharge Device(Elsevier, 2018) Connors, Bret A.; Schaefer, Ray B.; Gallagher, John J.; Johnson, Cynthia D.; Li, Guangyan; Handa, Rajash K.; Evan, Andrew P.; Anatomy and Cell Biology, School of MedicineObjective To determine if an innovative extracorporeal electrohydraulic shock wave device (sparker array) can effectively fracture artificial stones in vitro and in vivo, and if sparker array treatment produces a renal lesion in our pig model of lithotripsy injury. Results of these experiments will be used to help evaluate the suitability of this device as a clinical lithotripter. Methods Utracal-30 artificial stones were placed in a holder at the focus of the sparker array and treated with 600 shock waves (21.6 kV, 60 shocks/min). Stone fragments were collected, dried and weighed to determine stone breakage. In vivo stone breakage entailed implanting stones into pigs. These stones were treated with 600 or 1200 shock waves and the fragments collected for analysis. Lesion analysis consisted of treating the left kidney of pigs with 1200 or 2400 shock waves and quantitating the hemorrhagic lesion. Results In vitro, 71±2% of each artificial stone was fractured to < 2 mm in size. In vivo stone breakage averaged 63%. Renal injury analysis revealed that only 1 out of 7 kidneys showed evidence of hemorrhagic injury in the treated area. Conclusions The sparker array consistently comminuted artificial stones demonstrating its ability to fracture stones like other lithotripters. Also, the sparker array caused little to no renal injury at the settings used in this study. These findings suggest further research is warranted to determine the potential of this device as a clinical lithotripter.Item Renal Protection Phenomenon Observed in a Porcine Model After Electromagnetic Lithotripsy Using a Treatment Pause(Mary Ann Liebert, Inc., 2021) Connors, Bret A.; Gardner, Tony; Liu, Ziyue; Lingeman, James E.; Williams, James C., Jr.; Anatomy, Cell Biology and Physiology, School of MedicinePurpose: Pretreating the kidney with 100 low-energy shock waves (SWs) with a time pause before delivering a clinical dose of SWs (Dornier HM-3, 2000 SWs, 24 kV, and 120 SWs/min) has been shown to significantly reduce the size of the hemorrhagic lesion produced in that treated kidney, compared to a protocol without pretreatment. It has been assumed that a similar reduction in injury will occur with lithotripters other than the HM-3, but experiments to confirm this assumption are lacking. In this study, we sought to verify that the lesion protection phenomenon also occurs in a lithotripter using an electromagnetic shock source and dry-head coupling. Materials and Methods: Eleven female pigs were placed in a Dornier Compact S lithotripter where the left kidney of each animal was targeted for lithotripsy treatment. Some kidneys received 2500 SWs at power level (PL) = 5 (120 SWs/min) while some kidneys were pretreated with 100 SWs at PL = 1, with a 3-minute time pause, followed immediately by 2500 SWs at PL = 5 (120 SWs/min). Lesion size analysis was performed to assess the volume of hemorrhagic tissue injury created by each treatment regimen (% functional renal volume). Results: Lesion size fell by 85% (p = 0.01) in the 100 SW pretreatment group compared to the injury produced by a regimen without pretreatment. Conclusions: The results suggest that the treatment pause protection phenomenon occurs with a Dornier Compact S, a machine distinctly different from the Dornier HM-3. This result also suggests that this phenomenon may be observed generally in SW lithotripters.