Browsing by Author "Johnson, Cynthia D."

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    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 Medicine
    Introduction 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.
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    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 Medicine
    We 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.
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    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 Medicine
    INTRODUCTION 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.
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    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 Medicine
    Objective 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.
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    Shock wave lithotripsy does not impair renal function in a Swine model of metabolic syndrome
    (Mary Ann Liebert, 2015-04) Handa, Rajash K.; Johnson, Cynthia D.; Connors, Bret A.; Evan, Andrew P.; Phillips, Carrie L.; Liu, Ziyue; Department of Anatomy & Cell Biology, IU School of Medicine
    PURPOSE: To determine whether shock wave lithotripsy (SWL) may be a risk factor for renal functional impairment in a swine model of metabolic syndrome (MetS). MATERIALS AND METHODS: Nine-month-old female Ossabaw pigs were fed an excess calorie atherogenic diet to induce MetS. At 15 months of age, the MetS pigs were treated with 2000 SWs or an overtreatment dose of 4000 SWs targeted at the upper pole calyx of the left kidney (24 kV at 120 SWs/min using the unmodified Dornier HM3 lithotripter; n=5-6 per treatment group). Serum creatinine (Cr) and blood urea nitrogen (BUN) levels were measured in conscious pigs before and ∼60 days after SWL to provide a qualitative assessment of how well both kidneys were filtering (glomerular filtration rate [GFR]). Bilateral renal function was assessed at ∼65 days post-SWL in anesthetized pigs with GFR and effective renal plasma flow (ERPF) quantified by the renal clearance of inulin and para-amino hippurate, respectively. RESULTS: Cr and BUN values were within normal limits before SWL and remained unchanged after lithotripsy in both the 2000 SW- and 4000 SW-treated pigs. GFR and ERPF of kidneys treated with SWL at either SW dose were similar to the contralateral nontreated kidney. Chronic histological changes in the SW-treated pole of the kidney included interstitial fibrosis, sclerotic glomeruli, and dilated and atrophic tubules. CONCLUSIONS: Our results are consistent with the view that a single SWL session does not result in renal impairment, even in the presence of MetS.
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    Shock wave lithotripsy targeting of the kidney and pancreas does not increase the severity of metabolic syndrome in a porcine model
    (Elsevier, 2014-10) Handa, Rajash K.; Evan, Andrew P.; Connors, Bret A.; Johnson, Cynthia D.; Liu, Ziyue; Alloosh, Mouhamad; Sturek, Michael; Evans-Molina, Carmella; Mandeville, Jessica A.; Gnessin, Ehud; Lingeman, James E.; Department of Anatomy & Cell Biology, IU School of Medicine
    PURPOSE: We determined whether shock wave lithotripsy of the kidney of pigs with metabolic syndrome would worsen glucose tolerance or increase the risk of diabetes mellitus. MATERIALS AND METHODS: Nine-month-old female Ossabaw miniature pigs were fed a hypercaloric atherogenic diet to induce metabolic syndrome. At age 15 months the pigs were treated with 2,000 or 4,000 shock waves (24 kV at 120 shock waves per minute) using an unmodified HM3 lithotripter (Dornier MedTech, Kennesaw, Georgia). Shock waves were targeted to the left kidney upper pole calyx to model treatment that would also expose the pancreatic tail to shock waves. The intravenous glucose tolerance test was done in conscious fasting pigs before lithotripsy, and 1 and 2 months after lithotripsy with blood samples taken for glucose and insulin measurement. RESULTS: Pigs fed the hypercaloric atherogenic diet were obese, dyslipidemic, insulin resistant and glucose intolerant, consistent with metabolic syndrome. Assessments of insulin resistance, glucose tolerance and pancreatic β cell function from fasting plasma glucose and insulin levels, and the glucose and insulin response profile to the intravenous glucose tolerance test were similar before and after lithotripsy. CONCLUSIONS: The metabolic syndrome status of pigs treated with shock wave lithotripsy was unchanged 2 months after kidney treatment with 2,000 high amplitude shock waves or overtreatment with 4,000 high amplitude shock waves. These findings do not support a single shock wave lithotripsy treatment of the kidney as a risk factor for the onset of diabetes mellitus.
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    Using 300 Pretreatment Shock Waves in a Voltage Ramping Protocol Can Significantly Reduce Tissue Injury During Extracorporeal Shock Wave Lithotripsy
    (Mary Ann Leibert, 2016-09-01) Connors, Bret A.; Evan, Andrew P.; Handa, Rajash K.; Blomgren, Philip M.; Johnson, Cynthia D.; Liu, Ziyue; Lingeman, James E.; Anatomy and Cell Biology, School of Medicine
    Purpose: Pretreating a pig kidney with 500 low-energy shock waves (SWs) before delivering a clinical dose of SWs (2000 SWs, 24 kV, 120 SWs/min) has been shown to significantly reduce the size of the hemorrhagic lesion produced in that treated kidney, compared with a protocol without pretreatment. However, since the time available for patient care is limited, we wanted to determine if fewer pretreatment SWs could be used in this protocol. As such, we tested if pretreating with 300 SWs can initiate the same reduction in renal lesion size as has been observed with 500 SWs., Materials and Methods: Fifteen female farm pigs were placed in an unmodified Dornier HM-3 lithotripter, where the left kidney of each animal was targeted for lithotripsy treatment. The kidneys received 300 SWs at 12 kV (120 SWs/min) followed immediately by 2000 SWs at 24 kV (120 SWs/min) focused on the lower pole. These kidneys were compared with kidneys given a clinical dose of SWs with 500 SW pretreatment, and without pretreatment. Renal function was measured both before and after SW exposure, and lesion size analysis was performed to assess the volume of hemorrhagic tissue injury (% functional renal volume, FRV) created by the 300 SW pretreatment regimen., Results: Glomerular filtration rate fell significantly in the 300 SW pretreatment group by 1 hour after lithotripsy treatment. For most animals, low-energy pretreatment with 300 SWs significantly reduced the size of the hemorrhagic injury (to 0.8% ± 0.4%FRV) compared with the injury produced by a typical clinical dose of SWs., Conclusions: The results suggest that 300 pretreatment SWs in a voltage ramping treatment regimen can initiate a protective response in the majority of treated kidneys and significantly reduce tissue injury in our model of lithotripsy injury.