Simple and Patlak models for myocardial blood flow measurements with nitrogen-13-ammonia and PET in humans.

UNLABELLED: The Simple and Patlak models for estimating myocardial blood flow with 13N-ammonia have become attractive for clinical applications with PET because of their simplicity and ease of implementation. However, these models are sensitive to factors such as the data acquisition times and data integration times, which can cause errors in the estimation of myocardial blood flow, as demonstrated in this study. Limiting the application of these models to specific conditions can minimize the errors. METHODS: Dynamic PET images of the uptake of 13N-ammonia in the heart were obtained in seven humans under rest and dipyridamole stress. Myocardial blood flow was estimated using the Simple and Patlak models for different data acquisition times and data integration times. Blood flow values were compared to flow values computed with the two-compartment model as a reference. RESULTS: Blood flow values calculated with the Simple and Patlak models during the first 2 min of data acquisition were closely correlated to the two-compartment model values. Longer acquisition times resulted in significant underestimation of blood flow for the Simple model. Long integration times of greater than 60 sec also resulted in significant underestimation of blood flow for both models. CONCLUSION: The Simple and Patlak models produce estimates of myocardial blood flow that are well correlated with the two-compartment model estimated blood flows for the integration time of 60 sec from 60 to 120 sec postinjection. Because of the errors associated with longer data acquisition times and longer integration times, use of these models should be limited to a well-documented data acquisition paradigm.

High-resolution cardiac PET in rabbits: imaging and quantitation of myocardial blood flow.

UNLABELLED: A high-resolution PET system for small animals was tested for its applicability to the investigation of regional myocardial blood flow (MBF) in rabbits. METHODS: Nineteen measurements were performed in 10 closed-chest anesthetized rabbits at baseline and during infusions of adenosine (0.2 mg/kg/min) and propranolol (0.20-1.20 mg slow infusion) to obtain a wide range of MBF. Myocardial blood flow was assessed both by dynamic 13N-ammonia PET and by colored microspheres. Blood was withdrawn directly from the femoral artery, and arterial 13N activity was measured by coincidence type gamma detection system for the input function. Nitrogen-13 myocardial uptake was calculated by dividing the myocardial 13N activity by the integral value of the input function. RESULTS: Three or four contiguous cross-sectional myocardial images were obtained after 13N-ammonia injection. The left ventricular wall and cardiac cavity were clearly visualized. Moreover, initial passage of the tracer through the heart was obtained with serial 10-sec PET images. Nitrogen-13 myocardial uptake correlated well with flow measured with microspheres (r = 0.88). CONCLUSION: Our cardiac PET system can be used for in vivo imaging and quantitation of MBF in small animals and may play an important role in the future study of animal models of cardiovascular diseases.

Uptakes and images of 38K in rabbit heart, kidney, and brain.

UNLABELLED: The purpose of this study was to evaluate the kinetics and image quality of positron-emitting 38K (half-life, 7.6 min) and high-resolution small-animal PET in the heart, kidney, and brain of rabbits. METHODS: Studies were performed with 18 closed-chest anesthetized rabbits at baseline and during infusions of adenosine (0.2 mg/kg/min) and propranolol (0.5-1.0 mg/kg intravenously) using high-resolution small-animal PET. 38K was injected intravenously and dynamic PET imaging of the heart, kidney, or brain was performed for 3 min. Colored microspheres were injected into the left ventricle to measure organ blood flow. Arterial blood was withdrawn directly from the femoral artery, and, after the animals were killed, 38K activities in each organ were measured directly with a well counter. Uptake of 38K was calculated by dividing the 38K activities in each organ by the integral of the input function. The extraction fraction of 38K was estimated by dividing the uptake of 38K in each organ by the organ blood flow, measured by microspheres. RESULTS: The left ventricular myocardium and kidney were clearly visualized, but there was no visual 38K uptake in the brain. For the heart, kidney, and brain, respectively, average blood flow was 2.91 +/- 1.29, 5.49 +/- 0.71, and 0.57 +/- 0.11 mL/min/g, and the extraction fraction of 38K at baseline was 0.55 +/- 0.13, 0.48 +/- 0.13, and 0.022 +/- 0004. The Renkin-Crone model fit the relation between myocardial extraction and flow under a wide range of myocardial blood flow (r = 0.89). CONCLUSION: 38K is a suitable tracer for noninvasively showing the potassium kinetics of the heart, kidney, and brain by PET imaging.

Subsequential telomerase activity in exfoliated urinary cells detects recurrent disease in bladder cancer after transurethral resection.

We assessed urinary telomerase activity in bladder cancer patients to provide additional information for monitoring after transurethral resection (TUR). Urinary telomerase activity was detected in 22/26 (84.6%) patients with known bladder tumor before TUR. Ten of 11 patients who were available for sequential follow-up examination had urinary telomerase activity before TUR. In 4 of the 10 patients, urinary telomerase activity disappeared following TUR with or without adjuvant intravesical therapy. Three of the remaining 6 patients had recurrent bladder tumors within three months after TUR. Urinary telomerase activity analysis from patients after TUR provides important information on microscopic recurrent bladder cancer.

Enhancing effect of taurine in the rat caudate spindle. II. Effect of bilateral 6-hydroxydopamine lesions of the nigro-striatal dopamine system.

Bilateral injections of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle of rats resulted in destruction of dopamine (DA) nerve terminals in the striatum. DA contents decreased to 16.8, 15.0 and 13.7% of control values on 3, 5 and 7 days after the lesions, respectively. The time course of the effect of 6-OHDA lesions on apomorphine (0.5 mg/kg, IV)-induced stereotypy was investigated as the index of the development of supersensitivity. Stereotypy was unchanged on 3 days, but was enhanced 5 and 7 days after 6-OHDA lesions. Therefore, the sensitivity of postsynaptic DA receptors for apomorphine did not change 3 days after 6-OHDA lesions, although the striatal DA was depleted. The effects of bilateral injections of taurine into the striatum on the rat caudate spindle were determined 3 days after 6-OHDA lesions. Taurine, at a dose of 30 micrograms, enhanced the spindle in sham-operated rats, but this enhancement was not seen after 6-OHDA lesions. Intravenous administration of apomorphine (0.5 mg/kg) to lesioned rats suppressed the spindle, and this effect was prevented by a lower dose (3 micrograms) of taurine. These results provide further evidence that taurine enhances the spindle, possibly by decreasing the activity of the nigro-striatal DA system at the pre- and postsynaptic sites.

Enhancing effect of taurine on the rat caudate spindle. I: Interaction of taurine with the nigro-striatal dopamine system.

We studied the effects of taurine on the caudate spindle in rats and compared the findings with those of gamma-aminobutyric acid (GABA) when these compounds were microinjected into the bilateral striatum. Three micrograms of taurine was without effect, whereas 10 and 30 micrograms of taurine enhanced the spindle in a dose-dependent manner. GABA (3-100 micrograms) had no significant effect. Apomorphine (0.5 mg/kg) and methamphetamine (0.5 mg/kg) given intravenously to pargyline-pretreated rats suppressed the spindle. The suppressing effects of these drugs were reduced by taurine (3 micrograms) at the dose which, per se, did not affect the spindle. These results suggest that taurine may decrease the activity of striatal dopaminergic neurons and enhance the caudate spindle.

[Experience in ESWL monotherapy using Lithostar--comparative study on the efficacy of standard-tube with C-tube].

Between October 1990 and April 1996, we treated 892 upper urinary tract stones with ESWL therapy using Lithostar (Siemens Medizinische Technik, Erlangen, Germany). In March 1993, the coupling head of lithotriptor was upgraded from "standard-tube" to "C-tube". The C-tube has approximately two times or more destructive energy and intensity than the standard-tube. In this study, we analyzed the clinical results according to type of coupling head in 713 cases treated by ESWL monotherapy and evaluated 3 months after the initial treatment. The overall success rate at 3 months after ESWL was 85% in the standard-tube cases and 93% in the C-tube cases; the stone-free rate was 72% and 82%, respectively. There were no cases in which had to be discontinued due to ESWL severe side effects. However, in 66.1% of the C-tube cases and 31.1% of the standard-tube cases, a sufficient destructive intensity could not be used because of pain. Within a group that received sufficient destructive intensity, the C-tube was able to reduce both duration of the procedure and the number of shots to two thirds of that of the standard-tube.

[Two cases of giant testicular tumor with widespread extension to the spermatic cord: usefulness of upfront chemotherapy].

The first case was a 55-year-old man with biopsy-proven seminoma of the left inguinal undescended testis. The tumor, 10 x 9 x 9 cm in size, with a calculated weight of 520 g invaded the left spermatic cord up to the level of the renal hilum and metastasized to the retroperitoneal lymph nodes (13 x 10 cm). The serum level of lactate dehydrogenase (LDH) and beta human chorionic gonadotropin (beta-hCG) was 3,669 U/l and 1.3 ng/ml, respectively. The second case was a 38-year-old man with non-seminoma of the left testis. The testicular tumor, 32 x 28 x 28 cm in size, with a calculated weight of 7,000 g invaded the left spermatic cord up to the level of the aortic-bifurcation and metastasized to the retroperitoneal and the left supraclavicular lymph nodes. The serum level of LDH, alphafetoprotein (AFP) and beta-hCG was 2,040 U/l, 240 ng/ml and 5.6 ng/ml, respectively. Both patients were initially treated with VIP chemotherapy (etoposide, ifomide and cis-platinum), 4 cycles for the 1st case and 3 for the 2nd, and followed by high orchiectomy and retroperitoneal lymph node dissection. Histologic section of all resected specimens revealed only necrosis and fibrosis. The patients have been free of recurrence for 15 and 13 months, respectively, after the operation. In the Japanese literature, 42 cases of giant testicular tumor (> 400 g) including these two cases have been reported. To our knowledge, our second case is the largest among the non-seminomatous tumors. For giant testicular tumor with extensive invasion to the spermatic cord, initial chemotherapy followed by surgical resection appears to be a better management.

[Successful multidisciplinary treatment for bladder cancer with priapism. A case report].

A 44-year-old man suspected of having transitional cell carcinoma (TCC) of the prostate was referred to our hospital. He had a painful semi-erect penis at his first visit. Then needle biopsy of the corpus cavernosum histologically revealed metastatic TCC. CT of the pelvis showed bilateral ureteral obstruction caused by the advanced tumor but no lymph node swelling was found. Under the diagnosis of prostatic TCC with penile metastasis, bilateral percutaneous nephrostomy followed by two courses of combination chemotherapy (IFEP regimen) was carried out, which resulted in the disappearance of priapism. Radical cystectomy with total penectomy was performed. The final pathological diagnosis was corrected to TCC of the urinary bladder with invasion to the prostate and metastasis of the corpus cavernosum and the right obturator lymph node. Enlargement of the prostate proved to be caused by glandular hyperplasia with atypical hyperplasia of the prostate gland. Three courses of adjvent IFEP chemotherapy was given post-operatively and he has been alive with no evidence of the disease for 10 months.

[Metastatic testicular tumor requiring inferior vena cava resection with polytetrafluoroethylene graft replacement: a case report].

A 31 year-old man with a biopsy-proved retroperiotoneal yolk sac tumor was referred to our clinic. Physical examination revealed a thum- tip sized left supra-clavicular mass, a huge right abdominal mass and a tiny hard mass of the right testis. On CT scan, the abdominal tumor, 13 cm in diameter, encircled the inferior vena cava. Serum levels of LDH, AFP and hCG-beta were 2,585 U/l, 19,922 ng/ml and 6.6 ng/ml, respectively. No visceral metastasis was found. Following the right high orchiectomy, 4 cycles of VIP chemotherapy consisting of ifosfamide, etoposide and cisplatin were given, which resulted in partial response of the retroperitoneal mass and complete regression of the supraculavicular node with normalization of all tumor markers. Thus, retroperitoneal lymph node dissection was carried out. Because of the marked adhesion to the tumor, the inferior vena cava was segmentally resected together with the tumor, which was followed by reconstruction of the vena cava using a 16 cm long polytetrafluoroethylene graft, since no collateral venous route was found on the pretreatment venacavography. Histologically, the tumor was nearly necrotic with mature teratoma in small part. Postoperative clinical course was uneventful except feeling of numbness at the right tip toe, and the inferior vena cava has been patent 18 months after the operation with no evidence of recurrence.

[Treatment results of VIP (etoposide, ifosfamide and cisplatin) chemotherapy as a first-line therapy in metastatic germ cell tumors].

PURPOSE: We investigated the effectiveness and toxicity of VIP therapy as a first-line chemotherapy for patients with metastatic germ cell tumor. PATIENTS AND METHODS: From March 1994 to October 1997, we treated 16 patients with VIP therapy consisting of etoposide (100 mg/m2), ifosfamide, (1.2 g/m2) and cisplatin (20 mg/m2), all of which were generally given daily for 5 consecutive days every 3 weeks. Of the 16 patients, 6 were classified into a good, 5 into an intermediate, and 5 into a poor prognostic group according to the International Germ Cell Consensus Classification. RESULTS: Thirteen patients (81%) achieved complete response with VIP alone or VIP plus surgery. Three-year survival rate was 100% in good and intermediate prognostic group, while 40% in poor prognostic group. Although all patients had Grade 3 or higher myelosuppression, the treatment was well tolerated and no patient died of treatment-related complications. CONCLUSIONS: VIP appears to be an effective and safe regimen as an induction chemotherapy for good and intermediate risk patients with germ cell tumor. However, more intensive regimen may be necessary for poor-risk patients.

[Relationship between static images of 13N ammonia positron emission tomography and left ventricular wall motion in patients with coronary artery disease].

Observed myocardial activities in static image of 13N ammonia positron emission tomography (PET) contains factors about not only myocardial blood flow but also wall motion, wall thickness and glutamine synthetase activity. Those factors may help to delineate myocardial viability in 13N ammonia static image. To assess the role of 13N ammonia static image in prediction of reversibility of regional wall motion abnormalities after revascularization, we studied 20 patients with coronary artery disease. Of these patients, 15 patients underwent successful coronary revascularization (8 PTCA, 7 CABG). Regional 13N concentration before revascularization was expressed as a percent of maximal myocardial concentration and compared with regional wall motion. Wall motion was assessed by visual analysis using left ventriculography. Regional myocardial 13N concentration in normal, hypokinetic, akinetic and dyskinetic segments was 85 +/- 9.3%, 75 +/- 11%*, 71 +/- 17%* and 58 +/- 7.7%*#+, respectively (*p < 0.05 vs. normal, #p < 0.05 vs. hypokinesis, +p < 0.05 vs. akinesis). The segments with functional improvement showed significantly higher concentration of 13N than those without functional recovery (80 +/- 9.7% vs. 67 +/- 8.3%, p < 0.05). By using an optimized threshold value for normalized 13N activities, the sensitivity and specificity reached to 67% and 100%, respectively, to predict functional recovery. Our data suggested that myocardial 13N concentration in static PET image is closely related to the left ventricular wall motion in the patients with coronary artery disease and that it has a possible value of prediction of myocardial viability.

Perirenal pseudolymphoma: a case report.

A right nephrectomy was performed on a 51 year-old female with a tumor surrounding the right kidney since the possibility of malignant lymphoma could not be excluded based on radiography or a needle biopsy. An immunohistological examination of the surgically-resected specimen confirmed a diagnosis of pseudolymphoma. A pseudolymphoma involving the urinary tract is rare, and this is only the second reported case of pseudolymphoma in the perirenal space.

Adenosine-induced coronary flow reserve in Watanabe heritable hyperlipidemic rabbits.

The Watanabe heritable hyperlipidemic (WHHL) rabbit develops coronary atherosclerosis and hypercholesterolemia because of a genetic deficiency of low-density lipoprotein receptors and is therefore a good animal model for studying the relationships of coronary atherosclerosis, hypercholesterolemia and coronary flow reserve. The aim of the present study was to assess myocardial perfusion at baseline and during adenosine infusion (0.2 mg x kg(-1) x min(-1)) in 8 WHHL rabbits (13.8+/-0.5 months) with 13N-ammonia, small-animal positron emission tomography (PET) and colored microspheres. Results were compared with those from 6 age-matched Japanese white rabbits. Plaque distribution was also examined in the extramural coronary arteries. All 8 WHHL rabbits had coronary plaques, with 6 showing multiple plaques. Mean global myocardial blood flow (ml x min(-1) x g(-1)) did not differ significantly between control and WHHL groups both at baseline (3.67+/-0.72 vs 4.26+/-1.12 ml x min(-1) x g(-1), p=NS) and with adenosine (7.92+/-2.00 vs 9.27+/-2.91 ml x min(-1) x g(-1), p=NS), nor did coronary flow reserve (2.16+/-0.37 vs 2.18+/-0.41, p=NS). None showed evidence of regional perfusion abnormalities by visual and semiquantitative analyses of PET images. It was concluded that WHHL rabbits preserve adenosine-induced coronary flow reserve despite coronary atherosclerosis and hypercholesterolemia, suggesting that a compensatory mechanism develops in this animal model.

Cone-beam CT angiography of the thorax: an experimental study.

The authors recently developed a cone-beam computed tomography (CT) scanner and this report presents their evaluation of its potential for thoracic vascular imaging. An X-ray tube and a video-fluoroscopic system were rotated around the objects and 360 projected images were collected in a 12-s scan. Each image was digitized and a 3 dimensional (D) image (256x256x256 voxel volume with a voxel dimension of 0.9x0.9x0.9 mm) was reconstructed. Two different 3D-CT angiographies were investigated in 2 pigs: right atriography and thoracic aortography. Each pig was anesthetized, mechanically ventilated and positioned within the scanner. Contrast agent was infused through the right atrium or the aortic root at a rate of 3 ml/s during the scan. The right atriography scan clearly delineated the anatomy of the pulmonary artery, heart chambers and thoracic aorta. The thoracic aortography scan also clearly delineated the aortic anatomy including the internal thoracic and intercostal arteries. In conclusion, cone-beam CT angiography is potentially useful for thoracic vascular imaging.

Effects of VA-045, a novel apovincaminic acid derivative, on age-related impairment evidence in electroencephalograph, caudate spindle, a passive avoidance task and cerebral blood flow in rats.

1. The ability of VA-045 to improve aged-related impairment on electroencephalograph (EEG), caudate spindle, performance on a passive avoidance task and cerebral blood flow (CBF) were evaluated in rats. 2. The cortical EEG of the aged rats showed a higher incidence of spontaneous spindle burst (SSB) than seen in young rats. VA-045 decreased the incidence of SSB in aged rats. In contrast, vinpocetine increased the incidence of SSB in aged rats. 3. Electrical stimulation of the striatum in aged rats lead to a higher incidence of neocortical high voltage spindle (CS) than seen in young rats. In young rats, VA-045 had no effect on the CS, whereas an age-related increase in CS was blocked by VA-045, but was enhanced by vinpocetine. 4. There were no differences in the cortical EEG arousal response elicited by stimulation of the reticular formation of the brain stem in rats of all ages. VA-045 and vinpocetine had no effect on the cortical EEG arousal response in both young and aged rats. 5. VA-045, but not vinpocetine, attenuated the age-related decreased step through latency (STL) on a passive avoidance task. VA-045 and vinpocetine did not enhance the acquisition of learning behavior in a passive avoidance task in young rats. 6. VA-045 increased the cerebral blood flow (CBF) in both young and aged rats and the potency in aged rats was greater than that in young rats. Vinpocetine had no effect on CBF in either young or aged rats. 7. The pharmacological effects of VA-045 on age-related neuronal dysfunction are discussed.