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Biomedical subjects

Peter L Choyke

Publications and source records attributed to Peter L Choyke.

At least 37 records · Page 2Linked to original sources

Estimation of the differential pressure at renal artery stenoses.

Atherosclerotic disease of the renal artery can lead to reduction in arterial caliber and ultimately to conditions including renovascular hypertension. Renal artery stenosis is conventionally assessed, using angiography, according to the severity of the stenosis. However, the severity of a stenosis is not a reliable indicator of functional significance, or associated differential pressure, of a stenosis. A methodology is proposed for estimation of the renal artery differential pressure (RADP) from MR imaging. Realistic computational fluid dynamics (CFD) models are constructed from MR angiography (MRA) and phase-contrast (PC) MR. The CFD model is constructed in a semiautomated manner from the MR images using the Isosurface Deformable Model (IDM) for surface reconstruction and a Marching Front algorithm for construction of the volumetric CFD mesh. Validation of RADP estimation was performed in a realistic physical flow-through model. Under steady flow, the CFD estimate of the differential pressure across a stenosis in the physical flow-through model differed by an average of 5.5 mmHg from transducer measurements of the pressure differential, for differential pressures less than 60 mmHg. These results demonstrate that accurate estimates of differential pressure at stenoses may be possible based only on structural and flow images.

Arteriosclerosis↗

MR evaluation of solid renal masses.

After diagnosis of a suspicious renal mass on ultrasound or CT, renal MR imaging typically is ordered to characterize the mass further, stage the mass, or resolve discordant ultrasound and CT results. MR imaging may also be ordered in cases in which ultrasound is poor or in instances in which contrast-enhanced CT may be ill advised.

Carcinoma, Renal Cell↗

Parenchymal sparing surgery for central renal tumors in patients with hereditary renal cancers.

PURPOSE: Nephron sparing surgery has become accepted surgical practice for removing of renal tumors. The resection of central lesions has been thought to be more surgically challenging than that of peripheral tumors. We analyzed our experience with renal preservation surgery in patients with small hereditary central renal tumors. MATERIALS AND METHODS: From 1992 to 2000 we performed 116 partial nephrectomies with 44 kidneys (38%) demonstrating central renal masses. Central renal tumors were defined radiologically as those completely encircled by parenchyma or transgressing the interpapillary line on computerized tomography. We compared this group to a similar series of 67 patients with hereditary renal cancer with only peripheral based tumors. RESULTS: Mean tumor size was 3.2 cm (range 1.5 to 7.5). Mean operative time was 352 minutes (range 70 to 830). Renal hypothermia and vascular clamping were used in 19 of 44 procedures (41%). Mean ischemic time was 55 minutes (range 16 to 143). Mean blood loss was 4.6 l (range 0.1 to 23). The complication rate was 23% (10 of 44 cases) and with 18% (8 of 44) directly related to surgical technique. The mean transfusion requirement was 6.7 U (range 0 to 32) and 12 of 44 procedures (27%) required no blood products. Mean preoperative and postoperative serum creatinine was 1.05 (range 0.6 to 1.8) and 1.08 mg/dl (range 0.6 to 2.1), respectively. Mean followup was 33.7 months. No metastasis developed during followup. CONCLUSIONS: Central renal tumors are a common manifestation of hereditary renal cell carcinoma. There was no statistical difference found between common operative parameters when central and peripheral nephron sparing surgeries were compared. However, mean operative blood loss and transfusion requirements were increased in the central tumor group.

Adolescent↗

The relationship between renal tumor size and metastases in patients with von Hippel-Lindau disease.

PURPOSE: Patients with von Hippel-Lindau disease are at risk for multiple, bilateral, recurrent renal tumors and metastases. We previously evaluated the relationship between tumor size and metastases in families with hereditary renal cancer. We update our findings with about twice the number of patients with von Hippel-Lindau disease. MATERIALS AND METHODS: Screening affected kindred or retrospective review of medical records identified 181 patients with von Hippel-Lindau disease and renal cell carcinoma. Patients with small tumors were followed with serial imaging until the largest tumor reached 3 cm, at which point surgery was recommended. Surgical resection was recommended to patients with tumors larger than 3 cm. Patients not undergoing screening often had large renal tumors. RESULTS: A total of 108 patients with von Hippel-Lindau disease and solid renal tumors on computerized tomography imaging smaller than 3 cm (group 1) were followed a mean of 58 months (range 0 to 244). Metastatic disease did not develop in any of these patients. Renal tumors larger than 3 cm developed in 73 patients with von Hippel-Lindau disease (group 2). Mean followup of group 2 was 72.9 months (range 0 to 321). The proportion of procedures that were nephron sparing was higher in group 1 than in group 2 (120 of 125 [97%] compared to 85 of 125 [69%], Fisher's exact test p <0.0001). Metastases developed in 20 of 73 (27.4%) patients in group 2. The frequency of renal tumor metastases increased with increasing tumor size. CONCLUSIONS: No renal tumor metastases were found in patients with renal tumors less than 3 cm in diameter. We advocate a 3 cm threshold for parenchymal sparing surgery in patients with von Hippel-Lindau disease to decrease the risk of metastatic disease while preserving renal function, avoiding or delaying the need for dialysis and/or renal transplant, and decreasing the number of operations which a patient may undergo. We stress the importance of early screening in the kindred of patients with von Hippel-Lindau disease and vigilant followup thereafter.

Adolescent↗

Early onset hereditary papillary renal carcinoma: germline missense mutations in the tyrosine kinase domain of the met proto-oncogene.

PURPOSE: Hereditary papillary renal carcinoma (HPRC) is characterized by a predisposition to multiple, bilateral papillary type 1 renal tumors caused by inherited activating missense mutations in the tyrosine kinase domain of the MET proto-oncogene. In the current study we evaluated the clinical phenotype and germline MET mutation of 3 new HPRC families. We describe the early onset clinical features of HPRC. MATERIALS AND METHODS: We identified new HPRC families of Italian (family 177), Spanish (family 223) and Cuban (family 268) descent. We evaluated their clinical features, performed MET mutation analysis by denaturing high performance liquid chromatography and DNA sequencing, and estimated age dependent penetrance and survival using Kaplan-Meier analysis. We characterized renal tumors by histology and fluorescence in situ hybridization. RESULTS: Identical germline MET c.3522G --> A mutations (V1110I) were identified in families 177 and 268 but no evidence of a founder effect was found. Affected members of family 223 carried a germline c.3906G --> C.3522G --> A MET mutation (V1238I). Age dependent penetrance but not survival was significantly earlier for the c.3522G -->A mutation than for the c.3906G --> A mutation in these HPRC families. Trisomy of chromosome 7 and papillary renal carcinoma type 1 histology were detected in papillary renal tumors. CONCLUSIONS: HPRC can occur in an early onset form. The median age for renal tumor development in these 3 HPRC families was 46 to 63 years. HPRC associated papillary renal tumors may be aggressive and metastasize, leading to mortality. Median survival age was 60 to 70 years. Families with identical germline mutations in MET do not always share a common ancestor. HPRC is characterized by germline mutations in MET and papillary type 1 renal tumor histology.

Adenocarcinoma, Papillary↗

Micro-MRI methods to detect renal cysts in mice.

BACKGROUND: Mouse models of disease, especially using transgenic and knockout technologies, are powerful tools to analyze the molecular basis of disease. We recently reported that a new dynamic micro-MRI method with dendrimer-based contrast agents can visualize renal structure and function in normal living mice and mice with acute renal failure. While MRI contrast enhancement is useful for detecting functional impairment of the kidneys, this technology has limitations in assessing morphologic changes, particularly cystic disease, because contrast-enhanced micro-MRI depicts cysts as low-intensity areas that cannot be distinguished from fibrotic foci. METHODS: In the current study, we evaluated if micro-MRI employing a new three-dimensional MR hydrography signal sequence [three-dimensional fast imaging employing steady-state acquisition (3D-FIESTA)] can visualize chronic cystic changes without any contrast agents. RESULTS: We were able to positively depict multiple renal cortical cysts of approximately 0.2 mm diameter in a mouse model of sickle cell disease and observe serial changes of renal cysts (>0.2 mm diameter) in cyclooxygenase-2 (COX-2) knockout mice during a 21/2-month period. Some cysts decreased in size over time. CONCLUSIONS: Micro-MRI with 3D-FIESTA can depict cyst formation in the diseased kidneys of living mice without injection of contrast agents.

Anemia, Sickle Cell↗

From the RSNA refresher courses: a practical approach to the cystic renal mass.

The pathologic and imaging features of the renal cyst have been well described. A fluid-filled lesion is considered a cystic mass (ie, not a simple cyst) when it has any of the following features: calcification, high attenuation (>20 HU) at computed tomography, signal intensity not typical of water at magnetic resonance imaging, septations, multiple locules, enhancement, wall thickening, or nodularity. There are two important causes of a cystic renal mass: a complicated simple cyst (eg, one with hemorrhage, infection, or ischemia) and cystic renal cell carcinoma. At radiologic evaluation of such masses, it is imperative that optimal imaging techniques be used. Masses with calcification, high attenuation or high signal intensity, or septations can be categorized as benign (no further evaluation required), as requiring follow-up (probably benign), or as requiring surgery. Lesions requiring surgery can be benign or malignant at microscopic examination. Lesions that are multiloculated or demonstrate enhancement, wall thickening, or nodularity usually require surgery. When multiple features are present (eg, calcification and enhancement), the mass should be managed according to its most aggressive feature. Likewise, when there are conflicting findings at evaluation with different imaging modalities, the mass should be managed according to the most aggressive finding.

Adult↗

Functional tumor imaging with dynamic contrast-enhanced magnetic resonance imaging.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is the acquisition of serial MRI images before, during, and after the administration of an MR contrast agent. Unlike conventional enhanced MRI, which simply provides a snapshot of enhancement at one point in time, DCE-MRI permits a fuller depiction of the wash-in and wash-out contrast kinetics within tumors, and thus provides insight into the nature of the bulk tissue properties. Such data is readily amenable to two-compartment pharmacokinetic modeling from which parameters based on the rates of exchange between the compartments can be generated. These parameters can be used to generate color-encoded images that aid in the visual assessment of tumors. DCE-MRI is used currently to characterize masses, stage tumors, and noninvasively monitor therapy. While DCE-MRI is in clinical use, there are also a number of limitations, including overlap between malignant and benign inflammatory tissue, failure to resolve microscopic disease, and the inconsistent predictive value of enhancement pattern with regard to clinical outcome. Current research focuses on improving understanding of the meaning of DCE-MRI at a molecular level, evaluating macromolecular and targeted contrast agents, and combining DCE-MRI with other physiologic imaging techniques such as positron emission tomography. Efforts to standardize DCE-MRI acquisition, analysis, and reporting methods will allow wider dissemination of this useful functional imaging technique.

Contrast Media↗

Comparison of dendrimer-based macromolecular contrast agents for dynamic micro-magnetic resonance lymphangiography.

Few methods are currently available to visualize the entire lymphatic system. A method known as micro-magnetic resonance lymphangiography (MRL), which employs a dendrimer-based MRI contrast agent (PAMAM-G8) and a clinical-grade 1.5T MRI instrument, was recently developed for use in mice. In the present study, three dendrimer-based MRI contrast agents (PAMAM-G8, DAB-G5, and PAMAM-G4) with different pharmacokinetic characteristics were compared to determine the best reagent to visualize the lymphatic system under physiological or pathological conditions. In addition, two established MRI contrast agents (Gadomer-17 and Gd-[DTPA]-dimeglumine (Magnevist)) were used as control agents. In experiments with mice, most of the deep lymphatic system was visualized by micro-MRL with all agents except Gd-[DTPA]-dimeglumine. PAMAM-G8 was best for visualizing lymphatic vessels, whereas DAB-G5 was better for visualizing lymph nodes. PAMAM-G4 was intermediate in character between PAMAM-G8 and DAB-G5, except in exhibiting a low background signal (especially in the liver). The lymphatic system was not clearly visualized with Gd-[DTPA]-dimeglumine; however, the lymph nodes were visualized with Gadomer-17, although not as well as with dendrimer-based agents. In conclusion, DAB-G5 and PAMAM-G4 can be used to identify lymph nodes and lymphatic vessels, respectively. Their rapid excretion makes these compounds potentially attractive for human use.

Animals↗

Imaging of hereditary renal cancer.

Over the past 5 years there have been dramatic developments in the extent of knowledge of hereditary renal cancers. In addition to VHL, which is associated with clear cell carcinoma, one can now list HPRC (associated with type I papillary renal cancer) and HLRCC (associated with type II papillary renal cancer). BHD and FRO are associated with chromophobe carcinoma and oncocytomas, although other histologic tumor types have been found in BHD. Medullary carcinoma of the kidney is associated with sickle cell trait. Although the genes associated with these tumors have been discovered, the exact mechanisms by which they cause renal cancer remain to be elucidated. It is quite likely that other genes also are involved in this process. Using VHL as an example, research is now underway on targeting mutant pVHL or excess HIF for diagnostic and therapeutic purposes. Understanding the mechanisms leading to cancer may open new targets of opportunity for drug development. This improved knowledge of the biogenetic pathways used to form tumors will impact the development of new therapeutic techniques for treating renal cancers in hereditary and nonhereditary forms of the disease.

Diagnostic Imaging↗

Imaging of angiogenesis: from microscope to clinic.

Advances in imaging are transforming our understanding of angiogenesis and the evaluation of drugs that stimulate or inhibit angiogenesis in preclinical models and human disease. Vascular imaging makes it possible to quantify the number and spacing of blood vessels, measure blood flow and vascular permeability, and analyze cellular and molecular abnormalities in blood vessel walls. Microscopic methods ranging from fluorescence, confocal and multiphoton microscopy to electron microscopic imaging are particularly useful for elucidating structural and functional abnormalities of angiogenic blood vessels. Magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), ultrasonography and optical imaging provide noninvasive, functionally relevant images of angiogenesis in animals and humans. An ongoing dilemma is, however, that microscopic methods provide their highest resolution on preserved tissue specimens, whereas clinical methods give images of living tissues deep within the body but at much lower resolution and specificity and generally cannot resolve vessels of the microcirculation. Future challenges include developing new imaging methods that can bridge this resolution gap and specifically identify angiogenic vessels. Another goal is to determine which microscopic techniques are the best benchmarks for interpreting clinical images. The importance of angiogenesis in cancer, chronic inflammatory diseases, age-related macular degeneration and reversal of ischemic heart and limb disease provides incentive for meeting these challenges.

Angiogenesis Inhibitors↗

Isosurfaces as deformable models for magnetic resonance angiography.

Vascular disease produces changes in lumenal shape evident in magnetic resonance angiography (MRA). However, quantification of vascular shape from MRA is problematic due to image artifacts. Prior deformable models for vascular surface reconstruction primarily resolve problems of initialization of the surface mesh. However, initialization can be obtained in a trivial manner for MRA using isosurfaces. We propose a methodology for deforming the isosurface to conform to the boundaries of objects in the image with minimal a priori assumptions of object shape. As in conventional methods, external forces attract the surface toward edges in the image. However, smoothing is produced by a moment that aligns the normals of adjacent surface triangles. Notably, the moment produces no translational motion of surface triangles. The deformable isosurface was applied to a digital phantom of a stenotic artery, to MRA of three renal arteries with atherosclerotic disease and MRA of one carotid artery with atherosclerotic disease. Results of the surface reconstruction from the deformable model were compared with conventional X-ray angiography for the renal arteries. Measurement of the degree of stenosis of the renal arteries was within 12% +/- 6%. The deformable model provided improvements over the isosurface in all cases in terms of measurement of the degree of stenosis or improving the surface smoothness.

Algorithms↗

Hereditary renal cancers.

Hereditary renal cancer syndromes can lead to multiple bilateral kidney tumors that occur at a younger age than do nonhereditary renal cancers. Imaging plays an important role in the diagnosis and management of these syndromes. During the past decade, several new hereditary renal syndromes have been discovered but are not yet widely known. Whereas previously, the list of hereditary renal cancers in adults included von Hippel-Lindau disease and a rare form of chromosomal translocation, the list now includes the following syndromes: tuberous sclerosis, hereditary papillary renal cancer, Birt-Hogg-Dubé syndrome, hereditary leiomyoma renal cell carcinoma, familial renal oncocytoma, hereditary nonpolyposis colon cancer, and medullary carcinoma of the kidney. In addition, a number of newly described but poorly understood syndromes are under investigation. Even at this early stage, it is clear that elucidation of the underlying genetic mutations that cause hereditary renal cancer syndromes will have profound implications for understanding the origins of nonhereditary renal tumors. These studies will likely culminate in a better understanding of the causes of renal cancer, its prevention, and, ultimately, its cure.

Carcinoma, Medullary↗

Functional magnetic resonance imaging in oncology for diagnosis and therapy monitoring.

Functional magnetic resonance imaging is rapidly evolving as a capable noninvasive assessment tool for oncology to improve diagnosis and to monitor therapy. Current clinical techniques are based on microcirculation imaging using extracellular low molecular weight contrast agents such as gadopentetate dimeglumine and analogues. The temporal evolution of the enhancement visualizes the angiogenic properties of lesions with regard to vascular density and permeability, heterogeneity, and changes during therapy.

Bone Neoplasms↗

MR angiography using steady-state free precession.

Contrast-enhanced MR angiography (CE-MRA) using steady-state free precession (SSFP) pulse sequences is described. Using SSFP, vascular structures can be visualized with high signal-to-noise ratio (SNR) at a substantial (delay) time after the initial arterial pass of contrast media. The peak blood SSFP signal was diminished by <20% 30 min after the initial administration of 0.2 mmol/kg of Gd-chelate. The proposed method allows a second opportunity to study arterial or venous structures with high image SNR and high spatial resolution. A mask subtraction scheme using spin echo SSFP-S(-) acquisition is also described to reduce stationary background signal from the delayed SSFP angiography images.

Adult↗

Intraoperative ultrasound aids in dissection during laparoscopic partial adrenalectomy.

PURPOSE: Adrenal cortical sparing surgery is a relatively new approach to adrenal tumors. Laparoscopic partial nephrectomy is a technically feasible but challenging operation. We describe the use of intraoperative ultrasound to facilitate laparoscopic partial nephrectomy in a population with a hereditary predisposition to multifocal pheochromocytoma. MATERIALS AND METHODS: All patients underwent a history, physical examination, serum and urine catecholamine determinations, abdominal computerized tomography-magnetic resonance imaging and metaiodobenzylguanidine scan. The adrenal gland was exposed using a standard 3 or 4 port approach. Intraoperative ultrasound was performed using a 7.5 MHz. 10 mm. transducer placed through a 12 mm. port. After imaging the whole gland and adjacent structures partial adrenalectomy was performed based on intraoperative ultrasound images using a harmonic scalpel or alternatively using a cut and sew technique that provided a 5 mm. margin. Tumors were removed intact and sent for pathological examination. RESULTS: Since 1998, 11 patients have undergone laparoscopic partial adrenalectomy. Intraoperative ultrasound was performed in 7 patients with suspected multiple adrenal masses, including 4 and 3 who underwent unilateral and bilateral laparoscopic partial nephrectomy, respectively. Six of the 7 patients had germline defects in the von Hippel-Lindau disease gene and 1 had no identifiable alteration in the von Hippel-Lindau disease or RET gene. A solitary tumor was identified in 3 cases and multiple lesions were noted in 4. In 1 case intraoperative ultrasound localized a tumor not identified on preoperative imaging that was not readily visible via laparoscopy. Intraoperative ultrasound guided surgical dissection in all cases and identified an extra-adrenal mass in 1 patient with bilateral adrenal masses. There were no complications due to intraoperative ultrasound and no conversions to open surgery. Mean operative time was 335 minutes and mean estimated blood loss was 179 ml. Histological study demonstrated pheochromocytoma in 14 lesions and the extra-adrenal mass proved to be a splenic rest. At short-term followup no recurrences have been noted. All patients retained sufficient adrenal cortical function to avoid steroid replacement therapy. CONCLUSIONS: Laparoscopic ultrasound differentiates normal adrenal parenchyma from adrenal tumors and facilitates laparoscopic partial adrenalectomy.

Adolescent↗