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PubMed1994

Isolated single lung perfusion with doxorubicin is effective in eradicating soft tissue sarcoma lung metastases in a rat model.

The only effective therapy for patients with metastatic soft tissue sarcoma in the lung is surgical resection, with a 5-year survival of approximately 25%. Because systemic chemotherapy has not significantly affected survival in these patients, we began to investigate locoregional chemotherapy. We have previously shown that isolated single lung perfusion with doxorubicin in the rat results in higher lung tissue levels and lower systemic toxicity than does high-dose intravenous therapy. In the present study, we examined the safety of isolated lung perfusion with doxorubicin and its efficacy in the treatment of experimental pulmonary metastases from soft tissue sarcoma. In experiment 1, 15 F344 rats were randomized into three groups (n = 5): group I had isolated left lung perfusion with doxorubicin 320 micrograms/ml in saline solution; group II had left isolated lung perfusion with doxorubicin 480 micrograms/ml and group III with doxorubicin 640 micrograms/ml. All perfusions with doxorubicin were at 0.5 ml/min for 10 minutes followed by perfusion of saline solution for 5 minutes. On day 21, all animals underwent right (contralateral) pneumonectomy and were observed for over 10 days. In experiment 2, two groups of F344 rats were injected intravenously with 10(7) viable methylcholanthrene-induced sarcoma cells on day 0. On day 7, group I (n = 12) had left isolated lung perfusion with saline solution only and group II (n = 15) had isolated lung perfusion with doxorubicin 320 micrograms/ml. On day 21, all animals were killed, and their lungs were stained for metastases. Routine histologic sections from three animals from group II were examined. In experiment 1, 80% of the animals in group I survived contralateral pneumonectomy. There were no survivors in groups II and III. In experiment 2, three animals died after isolated lung perfusion (one from group I and two from group II), and one animal (group I) was excluded because of mediastinal tumor. All animals in both groups had massive tumor replacement of the right (untreated) lung. Group I animals had massive tumor replacement of the left (treated) lung, whereas animals in group II had eradication of metastases in nine of ten cases; no microscopic evidence of tumor was detected in all three animals evaluated for microscopic disease. Isolated lung perfusion with doxorubicin 320 micrograms/ml is safe and effective in eradicating experimental pulmonary sarcoma metastases in this model.

Animals↗

PubMed1998

Disposition and covalent binding of diflunisal and diflunisal acyl glucuronide in the isolated perfused rat liver.

Acyl glucuronides are intrinsically reactive metabolites of carboxylate drugs, capable of undergoing hydrolysis, intramolecular rearrangement (isomerization via acyl migration), and intermolecular transacylation reactions. Transacylation with nucleophilic groups located on protein molecules leads to covalent drug-protein adducts. Protein adducts can also form from the rearrangement isomers via a glycation mechanism. In this study, the isolated perfused rat liver preparation was used to separately trace the dispositions of the nonsteroidal anti-inflammatory drug diflunisal (DF), its reactive acyl glucuronide metabolite (DAG), and a mixture of DAG rearrangement isomers (iso-DAG), each administered at 30-microg DF equivalents/ml perfusate (four recirculating perfusions each group). After administration of DF, the drug was eliminated in a log linear manner over 3 hr, with apparent elimination half-life (t1/2) of 2.6 +/- 0.4 hr. The sulfate conjugate (DS), excreted almost exclusively into perfusate, accounted for 14.2% of the dose, with the phenolic glucuronide (DPG) and DAG (11.1 and 7.9% of dose, respectively) excreted primarily in bile. Only a small portion (2.3%) of the dose was recovered as novel "diglucuronides" (D-2G, arising from phenolic glucuronidation of iso-DAG), excreted exclusively in bile. Covalent DF-protein adducts were found in both perfusate (0.98%) and liver (0. 14%). After administration of DAG, rapid hydrolysis occurred (initial DAG t1/2 17.3 +/- 4.2 min). At 3 hr, recoveries (in comparison to DF-dosed perfusions) were similar for DF (51.7%) and DAG (8.3%), significantly decreased for DS (10.6%) and DPG (6.4%), and significantly increased for iso-DAG (0.8%), D-2G (9.1%), and covalent adducts in perfusate (1.49%) and liver (0.30%). After administration of iso-DAG, elimination from perfusate was slower (t1/2 55 +/- 15 min), and hydrolysis to DF was modest by comparison with DAG-dosed perfusions. Recoveries as iso-DAG and D-2G in bile were greatly enhanced (8.2 and 36.4%, respectively). Adduct formation was higher in liver (0.76% of dose) but not in perfusate (1.03%). Immunoblots of liver homogenates revealed drug-modified proteins at ca. 110 and 120 kDa. The results show that (a) DAG undergoes avid systemic deconjugation-conjugation cycling and isomerization to iso-DAG; (b) iso-DAG is more resistant to hydrolysis, is readily taken up by hepatocytes and undergoes novel metabolism (phenolic glucuronidation); and (c) the glycation pathway (i.e. using iso-DAG as substrate) plays a major role in formation of covalent DF-protein adducts in liver.

Animals↗

PubMed1998

Recovery of sheep hearts after perfusion preservation or static storage with crystalloid media.

BACKGROUND: These experiments were designed to evaluate the viability of large hearts after preservation by use of procedures that have shown good results with small animal hearts. Efficacy of novel long-term preservation protocols should be documented with a large animal model before such procedures can be adopted for clinical use. We studied the recovery of sheep hearts that were perfusion-preserved in media containing two different substrate mixtures and hearts stored without perfusion either in University of Wisconsin solution modified to maintain tissue adenosine triphosphate content or in Stanford solution. METHODS: Six groups of sheep hearts were studied: I, fresh nonpreserved controls; II, hearts perfusion-preserved at 11 degrees C for 24 hours by use of an oxygenated extracellular-type medium with pyruvate + glucose substrate; III, hearts preserved as for II but with aspartate + glutamate + glucose substrate; IV, hearts stored without perfusion at 3 degrees C for 24 hours in University of Wisconsin solution containing 2,3-butanedione monoxime 30 mmol/L, CaCl2 1 mmol/L, and fresh reduced glutathione 3 mmol/L; V, hearts stored without perfusion at 3 degrees C for 4 hours in Stanford solution; VI, hearts preserved as for II but without perfusion. Recovery was measured for 6 hours in a Langendorff model, perfused with an erythrocyte + albumin medium. RESULTS: Hearts that were perfusion-preserved with both substrate mixtures and hearts stored in modified University of Wisconsin solution recovered function that was not significantly different from control subjects. Hearts stored in Stanford medium did not recover as well as did groups II, III, and IV. Left ventricular pressure and peak rate of left ventricular relaxation of the Stanford group were lower, and left ventricular enddiastolic pressure was higher, than those values for controls (repeated measures analysis of variance; Dunnett's procedure). The group VI hearts did not recover function at all. CONCLUSION: The results suggest that large hearts preserved with medium containing either aspartate + glutamate + glucose or pyruvate + glucose have comparable recovery after long-term perfusion preservation. Aspartate + glutamate may offer advantages for clinical use because of their lower production of lactate and better chemical stability compared with pyruvate. Static storage in modified University of Wisconsin solution also produced viable hearts with recovery comparable to perfusion-preserved aspartate + glutamate + glucose hearts. Tests of these preservation media and procedures with large transplanted hearts are warranted.

Animals↗

PubMed2000

Hemodynamic assessment of acute stroke using dynamic single-slice computed tomographic perfusion imaging.

BACKGROUND: Stroke management would benefit from a broadly available imaging tool that detects perfusion deficits in patients with acute stroke. OBJECTIVE: To determine the role of dynamic, single-slice computed tomographic (CT) perfusion imaging (CTP) in the assessment of acute middle cerebral artery stroke. DESIGN AND PATIENTS: Imaging with CTP and CT within the first 6 hours of symptom onset and before the start of treatment in a consecutive clinical series of 22 patients (mean age, 68.3 years; 14 women; studied within 143 +/- 96 minutes of stroke onset). SETTING: A stroke unit in a university hospital. MAIN OUTCOME MEASURES: Area of the perfusion deficit (nAP(0)) from time-to-peak maps, hemispheric lesion area from follow-up CT (HLA(F)), final infarct volume, and stroke recovery (National Institutes of Health Stroke Scale scores). RESULTS: Eighteen patients had perfusion deficits in the middle cerebral artery territory and corresponding hypoattenuation in follow-up CT. Three patients with normal CTP findings showed lacunar infarctions or normal findings on follow-up CT. In 1 patient, CTP did not reveal a territorial deficit above the imaging slice. The overall sensitivity and specificity of CTP for the detection of perfusion deficits in patients with proven territorial infarction (n = 18) on follow-up CT were 95% and 100%, respectively. The nAP(0) was significantly correlated with the National Institutes of Health Stroke Scale score at admission (P<.003) and the HLA(F) (P<.001). Different stroke patterns were identified in patients with follow-up CTP (n = 10): (1) initial perfusion deficit and partial nutritional reperfusion (nAP(0)>HLA(F); n = 6), (2) initial perfusion deficit and nonnutritional reperfusion (nAP( 0)>/=HLA(F); n = 2), and (3) initial perfusion deficit without reperfusion (nAP(0)>/=HLA(F); n = 2). CONCLUSIONS: Computed tomographic perfusion imaging detects major perfusion deficits in the middle cerebral artery territory. Because CTP is broadly available, it may play a role in acute stroke management. Arch Neurol. 2000;57:1161-1166

Acute Disease↗

PubMed1997

Perfusion to colorectal cancer liver metastases is not uniform and depends on tumor location and feeding vessel.

Future effective therapies for hepatic metastases may depend on a better understanding of perfusion to these tumors. The purpose of this project was to define blood flow to colorectal cancer liver metastases using quantitative autoradiography (QAR). Liver tumors were established in F1 hybrids of WF x BN rats by intrasplenic injection of a DMH-induced rat colon adenocarcinoma. Rats underwent laparotomy 4-5 weeks later and [14C]iodoantipyrine (a radiotracer) was infused via the hepatic artery (HA) or portal vein (PV). Livers were harvested, frozen in liquid nitrogen, and sectioned at 20 microns through all tumors. QAR compared optical density of cross sections of tumors to surrounding normal liver tissue. Tumor:liver perfusion ratios (T/L PR) and tumor center:tumor periphery perfusion ratios (C/P PR) were calculated. All groups were analyzed with regard to tumor location and size. Seventy-seven tumors in 6 rats in the HA infusion group were analyzed; 74 tumors in 8 rats in the PV group were analyzed. Statistical analysis was by repeated measures analysis of variance. Mean HA T/L PR = 0.97 +/- 0.13, mean PV T/L PR = 0.25 +/- 0.11. Mean HA T/L PR for deep tumors was 1.38 +/- 0.17 and for superficial tumors was 0.57 +/- 0.15 (P < 0.01). Mean HA T/L PR for small tumors was 1.09 +/- 0.12 and for large tumors was 0.86 +/- 0.21 (P = 0.27). Mean PV T/L PR for deep tumors was 0.27 +/- 0.14 and for superficial tumors was 0.24 +/- 0.15 (P = 0.71). Mean PV T/L PR for small tumors was 0.31 +/- 0.15 and for large tumors was 0.20 +/- 0.14 (P = 0.54). Mean HA C/P PR = 1.15 +/- 0.15, mean PV C/P PR = 0.81 +/- 0.14 (P = 0.06). Mean HA C/P PR for small tumors was 1.37 +/- 0.16 and for large tumors was 0.92 +/- 0.17 (P = 0.01). Mean PV C/P PR for small tumors was 0.78 +/- 0.18 and for large tumors was 0.72 +/- 0.13 (P = 0.71). HA perfusion of tumors is significantly higher than PV perfusion compared to surrounding normal liver tissue. HA perfusion varies significantly depending on tumor location. There was a trend toward HA perfusion to the tumor center being slightly greater than to the periphery whereas the reverse was seen for PV perfusion. Tumor size did not affect overall perfusion but it did affect regional HA tumor perfusion.

Adenocarcinoma↗

PubMed1992

The nucleotide metabolism in lactate perfused hearts under ischaemic and reperfused conditions.

It was examined whether lactate influences postischaemic hemodynamic recovery as a function of the duration of ischaemia and whether changes in high-energy phosphate metabolism under ischaemic and reperfused conditions could be held responsible for impairment of cardiac function. To this end, isolated working rat hearts were perfused with either glucose (11 mM), glucose (11 mM) plus lactate (5 mM) or glucose (11 mM) plus pyruvate (5 mM). The extent of ischaemic injury was varied by changing the intervals of ischaemia, i.e. 15, 30 and 45 min. Perfusion by lactate evoked marked depression of functional recovery after 30 min of ischaemia. Perfusion by pyruvate resulted in marked decline of cardiac function after 45 min of ischaemia, while in glucose perfused hearts hemodynamic performance was still recovered to some extent after 45 min of ischaemia. Hence, lactate accelerates postischaemic hemodynamic impairment compared to glucose and pyruvate. The marked decline in functional recovery of the lactate perfused hearts cannot be ascribed to the extent of degradation of high-energy phosphates during ischaemia as compared to glucose and pyruvate perfused hearts. Glycolytic ATP formation (evaluated by the rate of lactate production) can neither be responsible for loss of cardiac function in the lactate perfused hearts. Moreover, failure of reenergization during reperfusion, the amount of nucleosides and oxypurines lost or the level of high-energy phosphates at the end of reperfusion cannot explain lactate-induced impairment. Alternatively, the accumulation of endogenous lactate may have contributed to ischaemic damage in the lactate perfused hearts after 30 min of ischaemia as it was higher in the lactate than in the glucose or pyruvate perfused hearts. It cannot be excluded that possible beneficial effects of the elevated glycolytic ATP formation during 15 to 30 min of ischaemia in the lactate perfused hearts are counterbalanced by the detrimental effects of lactate accumulation.

Adenosine↗

PubMedDate not supplied

Combined assessment of regional perfusion and wall motion in patients with coronary artery disease with technetium 99m tetrofosmin.

BACKGROUND: Technetium 99m tetrofosmin is a new 99mTc-labeled myocardial perfusion agent that can be labeled easily and provides excellent myocardial perfusion images. In addition, bolus administration of the tracer allows first-pass radionuclide ventriculography. METHODS AND RESULTS: This study examined the diagnostic value of combined assessment of regional perfusion by tetrofosmin tomography and wall motion by first-pass radionuclide ventriculography both at rest and during stress in 24 patients suspected of having coronary artery disease. All patients underwent stress-rest tetrofosmin tomography, stress-delayed thallium 201 tomography, and coronary angiography. Stress tetrofosmin tomography showed abnormal perfusion in all 23 patients with angiographic evidence of coronary artery disease, whereas stress 201Tl tomography showed abnormal perfusion in 22 of the 23 patients. For detection of significant (> or = 50% diameter stenosis) stenotic coronary arteries, the two perfusion studies showed similar sensitivities (62% with 201Tl and 69% with tetrofosmin) and specificities (88% and 100%, respectively). When analysis of regional wall motion was combined with perfusion study, a slightly higher sensitivity was obtained (77%), with similar specificity. The regional wall motion score was concordant with the regional perfusion score in only 42% of the segments at rest and 50% during exercise. CONCLUSIONS: These results suggest that stress tetrofosmin perfusion tomography and stress 201Tl tomography provided similar diagnostic accuracy for detection of coronary artery disease. The combined assessment of perfusion and function that is feasible with tetrofosmin may enhance diagnostic accuracy in patients with coronary artery disease.

Aged↗

PubMed2003

Regional differences between 99mTc-ECD and 99mTc-HMPAO SPET in perfusion changes with age and gender in healthy adults.

A number of studies using single-photon emission tomography (SPET) have shown perfusion changes with age in several cortical and subcortical areas, which might distort the results of perfusion imaging studies of neuropsychiatric disorders. Technetium-99m labelled ethyl cysteinate dimer (ECD) and hexamethylpropylene amine oxime (HMPAO) are both used as markers of cerebral perfusion, but have different pharmacokinetics and retention patterns. The aim of this study was to determine whether age and gender effects on perfusion SPET differ depending on whether (99m)Tc-HMPAO or (99m)Tc-ECD is used. Forty-five subjects (20 male and 25 female, mean age 52.8+/-6.6 years) were assigned to (99m)Tc-HMPAO SPET (HMPAO group), and 39 subjects (24 male and 15 female, mean age 52.6+/-6.7 years) to (99m)Tc-ECD SPET (ECD group). SPET images were obtained about 10 min after intravenous injection of approximately 800 MBq (99m)Tc-HMPAO or (99m)Tc-ECD using the same SPET scanner. Three-dimensional volumetric magnetic resonance imaging was performed to as7sess morphological changes in the grey matter. All image processing and statistical analyses were performed using SPM99 software. An area in the right anterior frontal lobe showed an increase in perfusion with age only in the HMPAO group, whereas areas in the bilateral retrosplenial cortex showed decreases in perfusion with age only in the ECD group; neither group showed corresponding changes in the grey matter. The present study shows that different effects of age on perfusion are observed depending on whether (99m)Tc-HMPAO and (99m)Tc-ECD is used. This suggests that the results of perfusion SPET are differently confounded depending on the tracer used, and that perfusion SPET with these tracers has limitations when used in research on subtle perfusion changes.

Age Factors↗

PubMed2003

Myocardial perfusion in type 2 diabetes with left ventricular hypertrophy: normalisation by acute angiotensin-converting enzyme inhibition.

The purpose of this study was to assess whether acute angiotensin-converting enzyme (ACE) inhibition would improve myocardial perfusion and perfusion reserve in a subpopulation of normotensive patients with diabetes and left ventricular hypertrophy (LVH), both independent risk factors of coronary disease. Using positron emission tomography (PET), we investigated the response of regional myocardial perfusion to acute ACE inhibition with i.v. infusion of perindoprilat (vs saline infusion as control, minimum interval 3 days) in 12 diabetic patients with LVH. Myocardial perfusion was quantified with PET using nitrogen-13 ammonia infused at rest and during dipyridamole hyperaemia. Twelve healthy control subjects were included in the study, five of whom were also studied with perindoprilat. Mean blood pressure in normo-albuminuric, asymptomatic patients was 123+/-7/65+/-9 mmHg. Compared with controls, maximal perfusion was reduced in patients (1.8+/-0.6 vs 2.5+/-1.0 ml min(-1) g(-1); P<0.05), and perfusion reserve was also lower, at borderline significance (2.7+/-1.0 vs 3.6+/-1.3; P=0.059). During perindoprilat infusion, myocardial perfusion reserve in patients increased to 3.9+/-0.9 ( P<0.001) due to normalisation of maximal perfusion (2.3+/-0.5 ml min(-1) g(-1), P<0.01). In the five control subjects both resting and hyperaemic perfusion remained unchanged during perindoprilat infusion. It is concluded that acute ACE inhibition with perindoprilat improves maximal achieved myocardial perfusion in non-hypertensive patients with diabetes and LVH.

Ammonia↗

PubMed2005

Simultaneous multi-section perfusion CT and CT angiography for the assessment of acute ischemic stroke.

BACKGROUND: Introduction of helical computed tomography (CT) scanning has enabled rapid imaging of the vascular status by means of CT angiography and perfusion CT. By virtue of recent multi-detector technology, helical CT has the ability to perform both CT angiography and multi-section perfusion CT simultaneously. This study investigated the clinical feasibility of simultaneous assessment of perfusion CT and CT angiography in patients with acute ischemic stroke. METHOD: Perfusion CT and CT angiography were performed simultaneously in a series of consecutive 31 acute ischemic stroke patients. The time required for the entire processing was about 15 minutes. Contrast agent was used in a total dose of 100 ml (35 ml for perfusion CT and 65 ml for CT angiography). FINDINGS: Simultaneous perfusion CT scans and CT angiographies were of diagnostic quality for 29 patients (94%). In large territorial infarct patients, perfusion CT could predict all perfusion deficits of the final lesions (10 out of 10 lesions) and CT angiography could detect 9 of 10 occlusions of major cerebral arteries (90%). In patients with small lacunar or subcortical infarcts, perfusion CT could predict 9 out of 19 lesions (47.4%), and false-negative were encountered in small lesions (three patients) or in inadequate coverage of data acquisition (seven patients). Acute stage thrombolytic intervention could be carried out based on the findings, and the success of thrombolytic therapy could be demonstrated by follow-up study. CONCLUSIONS: Simultaneous perfusion CT and CT angiography is the very useful tool for the rapid and adequate diagnosis of almost all of the large territorial infarcts and some of non-territorial lacunar infarcts. It is an easy-to-perform and safe imaging technique to assess acute ischemic stroke.

Acute Disease↗

PubMed1986

Alterations in perfused capillary morphometry in awake vs anesthetized brain.

This study quantitatively compared various indices of perfused capillary morphometry in pentobarbital-anesthetized and awake rat brains. We hypothesized that barbiturate anesthesia would reduce intraregional differences in percent perfused capillary volume and surface area. A high-molecular-weight FITC-labeled Dextran was injected intravenously into awake or barbiturate-anesthetized (50 mg/kg i.p.) rats. After 20 s, the animal was decapitated and the head frozen in liquid N2. Nine brain regions were isolated and mounted in a microtome cryostat. Sections, 2 microns thick, were photographed with a fluorescent microscope to detect the perfused capillaries. The sections were stained for alkaline phosphatase to visualize the total capillary network. Standard morphometric techniques were employed to determine the total and perfused volume (Vv), surface area (Sv) per mm3 and diameter (D) from the photographs. There were no significant differences in any index of total capillary morphometry among the regions in the anesthetized brain. Approximately half of the average total capillary bed was perfused and there were no significant differences in percent perfused Vv or Sv between awake and anesthetized brains. There were significant differences among the various brain regions in the perfused capillary bed of the awake rat. The percent perfused capillary Vv and Sv in the awake rat was significantly greater in the thalamus and anterior cortex than in other brain regions. In awake rats, the percent perfused capillary Vv ranged from 67.9 +/- 4.7% (mean +/- S.E.M.) in the thalamus to 26.1 +/- 4.3% in the posterior cortex. Thus, while the average percent perfused indices of capillary morphometry were not altered by anesthesia, regional differences in these indices among the examined regions were abolished with anesthesia.

Anesthesia, General↗

PubMed1992

Uneven perfusion within single cat muscles: nitric oxide and citrate synthase play no role.

There is an unexplained, marked regional heterogeneity in perfusion within single skeletal muscles both in dogs and rabbits. We asked if a similar distribution of perfusion was present within cat muscles. If present, we wanted to assess the possible roles of nitric oxide (NO) mediated vasodilation and citrate synthase (CS) activity for the regulation of this perfusion pattern. Perfusion was determined in 0.25 g regions within the gastrocnemius muscles by trapping of microspheres. We studied awake or anesthetized cats before and during inhibition of NO-formation using N-monomethyl-L-arginine. The CS activity was determined in homogenates of these regions. The coefficient of variation corrected for the Poisson distribution of microspheres (CVc) for the regional perfusion averaged 0.39. Despite a 25% reduction in perfusion to the whole muscles as compared to control, the uneven distribution of perfusion was not affected by blocking NO formation. Regional perfusion was not correlated to regional CS activity. Even if the regional distribution of CS activity also showed a scatter, mean coefficient of variation corrected for methodological error = 0.20, it was markedly less than that for perfusion. We conclude that neither NO vasodilation nor CS activity play an important role in the regulation of the regional perfusion pattern within single cat muscles.

Anesthesia↗

PubMed1994

The effect of positive end-expiratory pressure on regional pulmonary perfusion during acute lung injury.

PURPOSE: To determine whether positive end-expiratory pressure (PEEP) would change the altered regional pulmonary perfusion pattern caused by oleic acid (OA)-induced acute lung injury was the aim of this study. Our hypothesis was that fixed intravascular obstruction would not be affected by PEEP, leaving the perfusion pattern unchanged if this was the principal cause of perfusion redistribution after lung injury. METHODS: Regional measurements of pulmonary perfusion and lung water concentration (LWC) were obtained both before and after lung injury and before and after PEEP (10 cm H2O) with the nuclear medicine imaging technique of positron emission tomography after injections of H2 15O in 7 supine anesthetized dogs. Four animals were also treated with meclofenamate to enhance perfusion redistribution after acute lung injury. RESULTS: The application of PEEP before lung injury did not significantly affect the regional perfusion pattern. After administration of OA, LWC increased and fractional flow (without PEEP) decreased to the most edematous lung regions, consistent with perfusion redistribution. With the reapplication of PEEP, the perfusion pattern reverted toward the baseline pattern. The magnitude of this effect was roughly proportional to the effect of PEEP on regional inflation (r = .53), as evidenced by changes in LWC. CONCLUSIONS: The reversibility with PEEP of the perfusion pattern caused by acute lung injury suggests that fixed intravascular obstruction is not the principal determinant of perfusion redistribution after OA-induced injury.

Acute Disease↗

PubMed2004

Statistical assessment of regional time-density measurement of myocardial perfusion.

RATIONALE AND OBJECTIVES: The measurement of time-density relationships of the myocardium in studies of magnetic resonance perfusion images is a clinical technique used in assessing myocardial perfusion. This article presents a new technique, allowing regional time-density measurement and display of myocardial perfusion with improved accuracy compared with traditional manual trace techniques. Moreover, a method using statistical methods to discriminate relative decreased perfusion regions that differ significantly from the normally perfused myocardial tissue is introduced. MATERIALS AND METHODS: Human datasets were obtained using a 1.5 T Signa Echospeed system (GE Medical Systems, Milwaukee, WI). The perfusion sequence was a 2D cardiac-gated fast gradient echo sequence with echo train readout, generating an in-plane pixel size of 1.46 mm2. Seven 10-mm-thick contiguous short axis tomographic slice images were obtained during a prolonged single breathhold. Data was collected at 30 time phases per slice image level during passage of 20 cc gadolinium contrast injected at a rate of 4-5 cc/sec into an antecubital vein. RESULTS: Dilution properties can be determined and displayed as color-encoded regions superimposed on the myocardial slice according to the area of interest. Time-density curves throughout the perfusion study can be generated. Moreover, displays of normal and decreased perfusion areas can be used as statistically enhanced diagnosis guides. CONCLUSION: This measurement, display, and diagnosis technique adds diagnostically important information to previous measurement and visualization techniques, providing enhanced detection and quantitative evaluation of regional deficits in myocardial contractility and perfusion, providing improved reliability and reproducibility of clinical diagnoses from MR-perfusion data.

Analysis of Variance↗

PubMed2004

Noninvasive determination of regional myocardial perfusion with first-pass magnetic resonance (MR) imaging.

RATIONALE AND OBJECTIVES: To develop a method to provide absolute values of regional myocardial perfusion by means of color maps, and to determine myocardial perfusion reserve using magnetic resonance imaging during the first pass of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). MATERIALS AND METHODS: The study population consisted of five patients with hypertrophic cardiomyopathy, two with dilated cardiomyopathy, four with coronary artery disease, and one with normal coronary arteries who presented with mildly abnormal electrocardiogram findings. For each heartbeat, six continuous slices were acquired during the first pass of Gd-DTPA (0.05 mmol/kg body weight) before and during adenosine triphosphate (ATP) **stress using an electrocardiogram-triggered fast low-angle shot (FLASH) sequence on a 1.5-T magnetic resonance unit. Myocardial perfusion images were created and displayed by means of a color scale. The parameters were calculated pixel by pixel, using the upslope method. Myocardial perfusion reserve was then calculated, as the quotient of myocardial perfusion during ATP stress and perfusion before ATP stress. RESULTS: Myocardial perfusion during ATP stress in patients with normal coronary arteries (n = 1) or after successful percutaneous coronary intervention (n = 2) was increased compared with that before ATP stress. However, the patients with coronary artery disease (n = 2) failed to show increased myocardial perfusion. The patients with hypertrophic cardiomyopathy showed increased myocardial perfusion during ATP stress, although two with dilated cardiomyopathy did not. CONCLUSION: Our new technique can provide absolute values of regional myocardial perfusion by means of color maps, and has potential for widespread use for evaluation of ischemic and other types of heart disease.

Adenosine Triphosphate↗

PubMed2006

Comparison of Tc-99m DTPA and Tc-99m MAG3 perfusion time-activity curves in patients with renal allograft dysfunction.

AIM: The perfusion time-activity curve on DTPA renal scintigraphy shows a peak and plateau pattern which is usually absent or less marked when using tubular agents such as MAG3. The exact mechanism that results in this difference between the two tracers is not well understood. A descending pattern on MAG3 has been proposed to be due to decreased extraction. In this study we compared the diagnostic utility of perfusion patterns obtained with DTPA and MAG3 among patients with renal allograft dysfunction. MATERIALS AND METHODS: This study included 48 patients with renal allograft dysfunction and 18 recipients with normal graft function. Every recipient had renal scintigraphy with Tc-99m MAG3 and Tc-99m DTPA 1 day apart. The second phase of the perfusion curve after the initial rise was classified as ascending, flat, or descending. In patients with a descending curve on DTPA study, we calculated the ratio of counts at peak perfusion to that at plateau (P:PL). Impaired perfusion was based on a deterioration of the peak-to-plateau pattern on DTPA and the presence of a flat-descending curve on MAG3. RESULTS: In patients with dysfunction, impaired perfusion was observed in 77% of DTPA and in 54% of MAG3 studies. A flat-descending curve on MAG3 was present in 44% of patients with normal graft function. By MAG3, 67% of acute rejection and 28% of chronic allograft nephropathy (CAN) cases showed deteriorated perfusion. The corresponding values for DTPA were 67% and 94%, respectively. A flat-ascending pattern on DTPA was more frequent in CAN than it was in acute rejection (33% and 17%, respectively). CONCLUSION: The sensitivity of DTPA perfusion pattern for diagnosing dysfunction was significantly greater than that for MAG3. Our results suggest that the major determinant of a curve pattern on DTPA or MAG3 study is the extraction relative to perfusion. Thus for patients with CAN, extraction is higher relative to perfusion, resulting in a lower P:PL ratio or an ascending curve on DTPA. Although the extraction of DTPA is less than that of MAG3, this level of extraction renders DTPA more sensitive to serial changes in renal function and pathophysiological mechanisms related to kidney function.

Acute Disease↗

PubMed1996

Myocardial contrast echocardiography in human beings: correlation of resting perfusion defects to sestamibi single photon emission computed tomography.

The presence of myocardial perfusion abnormalities is generally accepted to suggest underlying coronary artery disease. In previous animal studies, myocardial contrast echocardiography (MCE) has been shown to be useful in delineating areas at risk after coronary occlusions. We sought to compare the presence or absence, size, and location of perfusion defects detected in human beings by MCE and sestamibi single photon emission computed tomography (SPECT). Regional wall motion was qualitatively assessed in the parasternal and apical views of a resting two-dimensional echocardiogram. Coronary angiography was performed in all patients and myocardial contrast echocardiography performed with 2 ml of intracoronary sonicated meglumine (Nycomed). A cine loop of the digitized contrast echocardiograms was used to analyze perfusion defects. Gated SPECT resting images in standard views were obtained after technetium 99m sestamibi (20 mCi) was administered. Visually perceived perfusion defects were established at 30% of maximal counts at end diastole. Perfusion defects by both techniques were planimetered, assigned to one of three perfusion artery territories, and expressed as a percentage of the perfusion territory studied. Comparison was made by linear regression analysis. Forty-one patients were studied. Perfusion defects were observed in 12 (29%) patients by MCE, 19 (46%) patients by SPECT, and 11 (27%) patients by both techniques. No perfusion defects were detected by MCE in 29 (70%) patients, by SPECT in 22 (53%) patients, or by either technique in 21 (51%) patients. The two techniques agreed in 78% of the patients. In 67 matching orthogonal views suitable for comparison between the two techniques, an 82% concordance for the presence or absence of defects was observed. The location of the defects matched in 86% of the cases. A significant correlation (p < 0.001; r = 0.62) between these techniques was observed in assessing the size of perfusion defects. In conclusion, our results suggest that MCE and sestamibi SPECT are comparable techniques for detecting severely underperfused myocardium in human beings.

Adult↗

PubMed1996

Correlation of poststenotic hyperemic coronary flow velocity and pressure with abnormal stress myocardial perfusion imaging in coronary artery disease.

The functional significance of coronary stenoses is frequently determined by adjunctive noninvasive myocardial perfusion imaging. Poststenotic coronary flow velocity and pressure can be measured directly during routine cardiac catheterization. The aim of this study was to correlate poststenotic (distal) flow velocity and pressure with stress perfusion imaging in patients. Quantitative angiography, basal and hyperemic transstenotic coronary flow velocities, and pressure gradients were measured in 50 patients within 1 week of exercise (n = 29) or of pharmacologic (n = 21) stress perfusion imaging. Twenty-two of 25 patients (88%) with reversible perfusion abnormalities had diminished distal coronary flow velocity reserves (CFVR) of < or = 2.0 x baseline, whereas 22 of 25 (88%) with normal perfusion imaging studies had a normal distal CFVR of > 2.0 (p = 0.000 1). Thirteen of 25 patients (52%) with reversible perfusion abnormalities had transstenotic gradients > or = 20 mm Hg, whereas 20 of 25 (80%) with normal perfusion studies had gradients <20 mm Hg (p = 0.01). Quantitative angiography did not differentiate patients with normal versus abnormal myocardial perfusion imaging. Distal CFVR was correlated more significantly with myocardial perfusion imaging results (kappa = 0.76) than with pressure gradients (kappa = 0.32). Exercise and pharmacologic stress myocardial perfusion imaging abnormalities reflect diminished post-stenotic coronary flow to a greater degree than transstenotic pressure gradients.

Adult↗