Retention and growth of urinary stones: insights from imaging

Recent work in nephrolithiasis has benefited from 2 special kinds of imaging: endoscopic study of patient kidneys with high-quality instruments, and examination of stones with microscopic computed tomography (micro CT). The combination of these has provided new evidence that there is more than 1 mechanism by which stones are retained in the kidney until they achieve sizes to be clinically relevant. This review describes what is known about the formation of stones on Randall's plaque, the formation of stones on ductal plugs and the ways in which stones may grow in free solution within the calyceal or pelvic spaces. Studies of urolithiasis need to recognize that any group of "stone formers" likely includes patients who differ fundamentally regarding which mechanism of stone formation is the primary route for their stones. Separation of patients on the basis of which mechanism (or combination of mechanisms) underlies their disease will be important for advancing research in the area of urolithiasis

Automated Detection of Coronal Loops using a Wavelet Transform Modulus Maxima Method

We propose and test a wavelet transform modulus maxima method for the au- tomated detection and extraction of coronal loops in extreme ultraviolet images of the solar corona. This method decomposes an image into a number of size scales and tracks enhanced power along each ridge corresponding to a coronal loop at each scale. We compare the results across scales and suggest the optimum set of parameters to maximise completeness while minimising detection of noise. For a test coronal image, we compare the global statistics (e.g., number of loops at each length) to previous automated coronal-loop detection algorithms

In vitro evaluation of the Lithoclast Ultra Vario combination lithotrite

Rigid intracorporeal lithotrites can be invaluable in the removal of large stone burdens during percutaneous nephrolithotomy. One such device, the Lithoclast Ultra Vario (LUV) has an outer ultrasound probe and inner pneumatic-ballistic probe. The ballistic probe can be advanced or retracted and run at 1-12 Hz. Since it can be difficult to predict optimal settings with any new device, we asked if in vitro testing could give insight into how best to operate this lithotrite. We tested the LUV under hands-free conditions that simulate treatment of fixed stones and freely movable stones. A fixed-stone test system measured the time to penetrate a gypsum model stone placed atop the probe and a movable-stone system determined time for comminution of a stone within a confined space. In addition, the time to evacuate 2-mm stone particles was measured. For hands-on testing, model stones were placed in a plastic dish submerged in water and the time to comminution was measured. Penetration time of fixed stones was faster with the ballistic probe extended 2.5 mm than when retracted (5.30 ± 0.85 vs. 8.75 ± 1.07 s, p < 0.0001). Comminution of free stones was faster with the ballistic probe retracted than when it was extended 1 mm or 2.5 mm (9.7 ± 0.9, 13.8 ± 1.3, 23.7 ± 3.2 s, p < 0.0001). In hands-on testing, extending the ballistic probe substantially reduced the efficiency of comminution (36.7 ± 6.4 vs. 131.3 ± 15.3 s, p < 0.0001). Clearance of fragments was considerably faster when the pneumatic-ballistic rate was 12 Hz compared to 1 Hz (12.3 ± 1.1 vs. 28.3 ± 2.2 s, p < 0.0001). These in vitro findings suggest ways to take advantage of the positive features while minimizing potential limitations of this lithotrite. Extending the ballistic probe is an advantage when the stone is immobile, as would be the case in treating a large stone that can be isolated against the wall of the pelvicalyceal system, but is a distinct disadvantage--due to retropulsion--when the stone is free to move. Operation of the LUV at fast ballistic rate significantly improved its ability to aspirate stone fragments

Mechanical haemolysis in shock wave lithotripsy (SWL): II. In vitro cell lysis due to shear

In this work we report injury to isolated red blood cells (RBCs) due to focused shock waves in a cavitation-free environment. The lithotripter-generated shock wave was refocused by a parabolic reflector. This refocused wave field had a tighter focus (smaller beam width and a higher amplitude) than the lithotripter wave field, as characterized by a membrane hydrophone. Cavitation was eliminated by applying overpressure to the fluid. A novel passive cavitation detector (HP-PCD) operating at high overpressure (up to 7 MPa) was used to measure acoustic emission due to bubble activity. The typical 'double-bang' emission measured in the lithotripter free-field was replaced by a continuum of weak signals when the fluid was enclosed in a pressure chamber. No acoustic emissions were measured above an overpressure of 5.5 MPa. Aluminium foils were used to study shock wave damage and had distinct deformation features corresponding to exposure conditions, i.e. pitting and denting accompanied by wrinkling. Pitting was eliminated by high overpressure and so was due to cavitation bubble collapse, whereas denting and wrinkling were caused by the reflected shock wave refocused by the parabolic reflector. RBCs suspended in phosphate-buffered saline (PBS) were exposed to the reflected wave field from a parabolic reflector and also from a flat reflector. Exposure to the wave field from the parabolic reflector increased haemolysis four-fold compared with untreated controls and was twice that of cell lysis with the flat reflector. Recently we analysed deformation and rupture of RBCs when subjected to a flow field set up by a focused shock. The cell lysis results presented here are in qualitative agreement with our theoretical prediction that haemolysis is directly related to the gradient of shock strength and validates shearing as a cell lysis mechanism in SWL

Effect of the body wall on lithotripter shock waves

PURPOSE: Determine the influence of passage through the body wall on the properties of lithotripter shock waves (SWs) and the characteristics of the acoustic field of an electromagnetic lithotripter. METHODS: Full-thickness ex vivo segments of pig abdominal wall were secured against the acoustic window of a test tank coupled to the lithotripter. A fiber-optic probe hydrophone was used to measure SW pressures, determine shock rise time, and map the acoustic field in the focal plane. RESULTS: Peak positive pressure on axis was attenuated roughly proportional to tissue thickness-approximately 6% per cm. Irregularities in the tissue path affected the symmetry of SW focusing, shifting the maximum peak positive pressure laterally by as much as ∼2 mm. Within the time resolution of the hydrophone (7-15 ns), shock rise time was unchanged, measuring ∼17-21 ns with and without tissue present. Mapping of the field showed no effect of the body wall on focal width, regardless of thickness of the body wall. CONCLUSIONS: Passage through the body wall has minimal effect on the characteristics of lithotripter SWs. Other than reducing pulse amplitude and having the potential to affect the symmetry of the focused wave, the body wall has little influence on the acoustic field. These findings help to validate laboratory assessment of lithotripter acoustic field and suggest that the properties of SWs in the body are much the same as have been measured in vitro

Design and characterization of a research electrohydraulic lithotripter patterned after the Dornier HM3

An electrohydraulic lithotripter has been designed that mimics the behavior of the Dornier HM3 extracorporeal shock wave lithotripter. The key mechanical and electrical properties of a clinical HM3 were measured and a design implemented to replicate these parameters. Three research lithotripters have been constructed on this design and are being used in a multi-institutional, multidisciplinary research program to determine the physical mechanisms of stone fragmentation and tissue damage in shock wave lithotripsy. The acoustic fields of the three research lithotripters and of two clinical Dornier HM3 lithotripters were measured with a PVDF membrane hydrophone. The peak positive pressure, peak negative pressure, pulse duration, and shock rise time of the focal waveforms were compared. Peak positive pressures varied from 25 MPa at a voltage setting of 12 kV to 40 MPa at 24 kV. The magnitude of the peak negative pressure varied from -7 to -12 MPa over the same voltage range. The spatial variations of the peak positive pressure and peak negative pressure were also compared. The focal region, as defined by the full width half maximum of the peak positive pressure, was 60 mm long in the axial direction and 10 mm wide in the lateral direction. The performance of the research lithotripters was found to be consistent at clinical firing rates (up to 3 Hz). The results indicated that pressure fields in the research lithotripters are equivalent to those generated by a clinical HM3 lithotripter

Using Helical CT to Predict Stone Fragility in Shock Wave Lithotripsy (SWL).

Great variability exists in the response of urinary stones to SWL, and this is true even for stones composed of the same mineral. Efforts have been made to predict stone fragility to shock waves using computed tomography (CT) patient images, but most work to date has focused on the use of stone CT number (i.e., Hounsfield units). This is an easy number to measure on a patient stone, but its value depends on a number of factors, including the relationship of the size of the stone to the resolution (i.e., the slicewidth) of the CT scan. Studies that have shown a relationship between stone CT number and failure in SWL are reviewed, and all are shown to suffer from error due to stone size, which was not accounted for in the use of Hounsfield unit values. Preliminary data are then presented for a study of calcium oxalate monohydrate (COM) stones, in which stone structure-rather than simple CT number values-is shown to correlate with fragility to shock waves. COM stones that were observed to have structure by micro CT (e.g., voids, apatite regions, unusual shapes) broke to completion in about half the number of shock waves required for COM stones that were observed to be homogeneous in structure by CT. This result suggests another direction for the use of CT in predicting success of SWL: the use of CT to view stone structure, rather than simply measuring stone CT number. Viewing stone structure by CT requires the use of different viewing windows than those typically used for examining patient scans, but much research to date indicates that stone structure can be observed in the clinical setting. Future clinical studies will need to be done to verify the relationship between stone structure observed by CT and stone fragility in SWL

Hyperplasia and Fluid Accumulation in Epithelial Cyst Formation and Growth

Epithelial cysts may develop in virtually any epithelium. All cysts, regardless of their origins, are characterized by epithelial hyperplasia and fluid accumulation. Additional features may include tubular atrophy, basement membrane alterations and association with inflammatory cells. In spite of the intense research effort in recent years directed at uncovering the cellular mechanisms of cyst development and growth, we still do not know the primary events that lead to cyst formation. However, there are at least three candidate mechanisms. These include: 1) increased cell proliferation (epithelial hyperplasia) in the cyst wall, 2) net fluid accumulation in the cyst cavity and 3) alterations of extracellular matrix components linked to cyst formation and growth. This review discusses the evidence to support the role of each mechanism as a possible primary event necessary for cyst initiation and continued enlargement. Present data on the pathogenesis of epithelial cyst formation strongly suggests that no single mechanism, as yet described, can adequately account for all situations of cyst occurrence

Progress in Lithotripsy Research

Shock wave lithotripsy (SWL) for the non-invasive treatment of kidney stones was introduced in the United States in 1984. SWL virtually eliminated the need for open surgery to remove kidney stones, and it did not take long for physicians and patients to endorse this revolutionary technology. Early reports told of the efficient removal of even the most troublesome stones without apparent complications, and SWL quickly became the "treatment modality of choice." It was not long, however, before concerned physicians began to report the occurrence of adverse effects in SWL, particularly involving vascular trauma and including cases of severe hemorrhage in the kidney and acute renal failure — significant side effects of serious consequence. Researchers quickly recognized the challenge and opportunity to determine the mechanisms of shock wave action in lithotripsy, and in 1988, the Acoustical Society of America held the first in a series of popular sessions devoted to the topic of shock waves in medicine. The goal of the inaugural session was to improve the fundamental understanding of lithotripsy — to bring better devices and treatments to patients. The goal of this paper is to report on progress in this effort

Reactive oxygen molecule-mediated injury in endothelial and renal tubular epithelial cells in vitro

Reactive oxygen molecule-mediated injury in endothelial and renal tubular epithelial cells in vitro. To investigate renal tubular epithelial cell injury mediated by reactive oxygen molecules and to explore the relative susceptibility of epithelial cells and endothelial cells to oxidant injury, we determined cell injury in human umbilical vein endothelial cells and in four renal tubular epithelial cell lines including LLC-PK1, MDCK, OK and normal human kidney Cortical epithelial cells (NHK-C). Cells were exposed to reactive oxygen molecules including superoxide anion, hydrogen peroxide and hydroxy 1 radical generated by xanthine oxidase and hypoxanthine. We determined early sublethal injury with efflux of 3H-adenine metabolites and a decline in ATP levels, while late lytic injury and cell detachment were determined by release of51 chromium. When the cells were exposed to 25, 50, and 100 mU/ml xanthine oxidase with 5.0mM hypoxanthine, ATP levels were significantly lower (P < 0.001) in LLC-PK1, NHK-C and OK cells compared to MDCK cells while ATP levels were significantly lower (P < 0.01) in endothelial cells compared to all tubular cell lines. A similar pattern of injury was seen with efflux of 3H-adenine metabolites. When the cells were exposed to 50 mU/ml xanthine oxidase with 5.0mM hypoxanthine for five hours, total 51chromium release was significantly (P < 0.001) greater in LLC-PK1, NHK-C and OK cells compared to MDCK cells, while total 51chromium release was significantly (P < 0.001) greater in endothelial cells compared to all tubular cells. However, lytic injury was the greatest in LLC-PK1 cells and NHK-C cells while cell detachment was the greatest in endothelial cells. MDCK cells were remarkably resistant to oxidant-mediated cell detachment and cell lysis. In addition, we determined ATP levels, 3H-adenine release and 51chromium release in LLC-PK1, NHK-C and endothelial cells in the presence of superoxide dismutase to dismute superoxide anion, catalase to metabolize hydrogen peroxide, DMPO to trap hydroxyl radical and DMTU to scavenge hydrogen peroxide and hydroxyl radical. We found that catalase and DMTU (scavengers of hydrogen peroxide) provided significant protection from ATP depletion, prevented efflux of 3H-adenine metabolites and cell detachment while DMPO (scavenger of hydroxyl radical) prevented lytic injury. In addition, we found that the membrane-permeable iron chelator, phenanthroline, and preincubation with deferoxamine prevented cell detachment and cell lysis, confirming the role of hydroxyl radical in cell injury. We conclude that among tubular epithelial cells, cells with proximal tubular characteristics including LLC-PK1, NHK-C and OK cells were more susceptible to oxidant injury than MDCK cells which originate from distal tubules. Endothelial cells responded to oxidant injury with a greater fall in ATP levels, efflux of 3H-adenine metabolites and cell detachment, while tubular epithelial cells demonstrated greater cell lysis. Finally, it appears that hydrogen peroxide mediates ATP depletion and efflux of 3H-adenine metabolites while hydrogen peroxide and hydroxyl radical mediate cell detachment and cell lysis