Stroke complicating adenosine perfusion imaging

Pharmacologic stress-testing using adenosine is increasing in popularity. Side-effects have been limited to the infusion time and a brief recovery period. Long-lasting complications may, however, result rarely.     

Cost-minimization analysis of intravenous adenosine and dipyridamole in thallous chloride TI 201 SPECT myocardial perfusion imaging

This paper deals with two patients with acetaminophen-induced pneumonitis. A 64-year-old woman suffered from mastitis while being treated by corticosteroid therapy for phemphigoid. She was administered antibiotics and acetaminophen. However, her fever continued and she subsequently developed dyspnea and interstitial pneumonia. The other patient, a 70-year-old woman, was treated with corticosteroid for lower motor neuron disease. Anti-GM1-IgM antibodies were positive in her serum. She developed wet cough and mild fever. During treatment with antibiotics and acetaminophen, her illness was complicated by dyspnea and interstital pneumonia. As a result of histological findings of transbronchial lung biopsy specimens showing interstitial infiltration of mononuclear cells, as well as clinical courses in which cessation of acetaminophen directly lead to the improvement of interstitial pneumonia, both patients were diagnosed to have acetaminophen-induced pneumonitis. The peumonitis responded well to steroid therapy. In vitro culture of peripheral lymphocytes showed stimulated proliferation by acetaminophen in both patients. These findings suggest that allergic mechanism was involved in the pathogenesis of the pneumonitis. Underlying immunological disorders may have enhanced the occurrence. Although acetaminophen is one of the most popular drugs because of a very low incidence of side effects, this drug should be applied carefully, especially with patients who have such immunological disorders.     

Rest or redistribution thallium myocardial imaging for resting myocardial perfusion: a detailed comparison with regional wall motion

Redistribution thallium-201 (201T1) imaging is the most common method of assessing resting myocardial perfusion. However, the equivalence of a redistribution image and a separate rest injection is unclear. Although the presence of a defect on rest imaging has normally been equated with the presence of a myocardial infarction, it has recently been shown that a significant proportion of fixed defects on exercise-redistribution 201T1 actually represent areas of viable myocardium. This study was a detailed comparison of rest and redistribution imaging in 30 patients undergoing routine exercise 201T1 scanning for the assessment of coronary artery disease. A small dose (15 MBq) of 201T1 was administered at rest following the imaging in three standard planar views. Similar stress images were acquired using a further 50-55 MBq of 201T1 administered at peak effort. Redistribution images were acquired 3-4 h later and equilibrium blood pool ventriculography performed using in vivo labelling with 600 MBq 99Tcm-pertechnetate. Of 150 abnormal segments on the exercise scans, 74 (49%) were identified as being reversible on the redistribution scans and 58 (39%) on the rest images. Only 39 (53%) of these reversible defects were identified on both the redistribution and rest scans. Only 41% of the fixed defects on the redistribution images (32% of fixed defects on the rest images) had abnormal wall motion. Therefore, rest and redistribution images are not equivalent. Both rest and redistribution images significantly overestimate myocardial infarction. This may have significant effects on patient selection for revascularization procedures and therefore all patients having perfusion scintigraphy should also have additional assessment of regional wall motion to allow accurate classification of the functional status of myocardial segments.     

New directions in myocardial perfusion imaging

In recent years, substantial progress has been made in the field of nuclear cardiology. Pharmacologic stress perfusion imaging with intravenous administration of dipyridamole or adenosine provides comparable sensitivity and specificity values for detection of coronary artery disease (CAD) as exercise imaging and has been employed successfully for risk stratification prior to peripheral vascular or aortic surgery and after myocardial infarction. Detection of myocardial viability can be enhanced utilizing reinjection of a second dose of thallium-201 (Tl-201) at rest after acquisition of redistribution images with the single photon emission computerized tomography (SPECT) technique. Imaging solely in the resting state with Tl-201 can also provide information concerning presence of viable myocardium in asynergic regions that are stunned or hibernating. New technetium-99m (Tc-99m) perfusion agents have emerged in the clinical setting and have provided excellent predictive value for detection of CAD in patients with chest pain and permit simultaneous assessment of function and regional blood flow. Tc-99m Sestamibi, one of these agents, is also a valid marker of viability when assessing myocardial salvage after coronary reperfusion in acute myocardial infarction.     

Motion and deformation tracking for short-axis echo-planar myocardial perfusion imaging

Aggression research does not lack data--it lacks a model for integrating data. One of the problems confronting aggression researchers is the extensive body of multidisciplinary data that is difficult to synthesize to generate new directions in research. This paper proposes one solution that starts by asking "what is the minimal number of categories of concepts and measurements which are necessary to describe a person?". The answer is four categories of concepts: biological; cognitive; behavioral; environmental (physical and social). One way of many for integrating these four categories of concepts is a proposed discipline neutral heuristic model that is used herein to compare two different research approaches to the study of impulsive aggression. This comparison identifies clearly the differences in the two approaches with regard to different emphases among the four categories of constructs for each program. Using the model an example of common ground between the two approaches is sought as a basis for extending aggression research. The main conclusion of one of the research programs was that central nervous arousal is related to impulsive aggression. This program demonstrated that phenytoin will reduce impulsive aggressive acts and has an effect on CNS arousal. The other research program on impulsive aggression has been at the forefront in demonstrating the well established inverse relationship between serotonin levels and aggression. The comparison resulted in the suggestion that both serotonin and phenytoin may relate to a common neurochemical substrate which interacts in part to control CNS arousal, especially at the cortical level. The proposed heuristic model made obvious the need to use synthesizing concepts (e.g. information processing or language) which can interrelate multidisciplinary concepts and data from different research programs within the four categories of constructs when comparing interdisciplinary research.     

Procedure guideline for myocardial perfusion imaging. Society of Nuclear Medicine

BACKGROUND AND PURPOSE: Parenterally administered MgSO4 is neuroprotective in standard animal models of focal cerebral ischemia and in many other paradigms of brain injury. Previous small clinical trials in stroke patients have explored the safety and tolerability of different infusion regimens. This study was undertaken to optimize the regimen for a multicenter trial. METHODS: Within 24 hours of the onset of clinically diagnosed stroke, patients were randomized to receive placebo or one of three intravenous MgSO4 infusions: a loading infusion of 8, 12, or 16 mmol, followed by 65 mmol over 24 hours. Cardiovascular parameters, serum magnesium concentrations, and blood glucose concentrations were determined. Outcome at 30 and 90 days was recorded. RESULTS: Twenty-five patients were recruited and treated at a mean time of 20 hours after stroke. No tolerability problems were identified. No effects of magnesium on heart rate, blood pressure, or blood glucose were evident. Serum magnesium concentrations rose to target levels most rapidly in the highest loading infusion group and were maintained in all groups for at least 24 hours. CONCLUSIONS: MgSO4 infusions that rapidly elevate the serum magnesium concentration to potentially therapeutic levels are well tolerated and have no major hemodynamic effects in patients with acute stroke. The 16-mmol loading infusion achieved target serum concentrations most rapidly and has been chosen for further trials.     

Correlates of unrecognized acute myocardial infarction detected via perfusion imaging

Research using the electrocardiogram (ECG) indicates that about 1/3 of acute myocardial infarctions (AMIs) are unrecognized. To date, no studies of unrecognized AMIs have employed perfusion imaging, although it is more sensitive than the ECG and provides more information about infarct characteristics, such as size and location. In this study, 82 of 258 consecutive patients (31.8%) undergoing exercise testing with technetium-99m sestamibi perfusion imaging had fixed, nonartifactual perfusion defects, suggesting AMI. These patients were interviewed regarding their recognition of AMI; 27 patients (32.9%) had unrecognized AMI. Unrecognized AMI was significantly associated with (1) smaller infarcts, (2) infarcts not in the apical or septal regions, (3) diabetes mellitus, (4) lack of angina, (5) a negative family history for cardiac disease, and (6) being African-American. Many of these variables were significantly intercorrelated, and in multivariate analysis, unrecognized AMI remained significantly predicted by a smaller infarct and lack of angina. This study suggests that the incidence of unrecognized AMI detected via perfusion imaging on a clinic population is similar to that detected via electrocardiographic studies on community samples. This study also replicates prior findings of the medical history and demographic correlates of unrecognized AMI, and indicates that infarct size and location are also associated with unrecognized AMI.     

Assessment of myocardial perfusion hemodynamics using echo planar MR imaging

It was possible to obtain images for individual heart beats using single-shot Echo Planar Imaging(EPI), and changes of myocardial signal intensity could be assessed visually after GD-DTPA administration. Measurement of the same site in the myocardium on myocardial perfusion images for individual heart beats was facilitated by imaging during breath-holding, and accurate evaluation was possible. In patients with coronary artery disease, the site of myocardial infarction tended to show less increase in signal intensity than the normal myocardium, and could easily be distinguished from normal myocardium according to the change in signal intensity. In patients with atrial fibrillation, the signal intensity of the myocardium varied with each heart beat, and it was difficult to assess perfusion hemodynamics. Myocardial perfusion studies using EPI still present problems with respect to spatial resolution, but the myocardial perfusion hemodynamics for individual heart beats can be determined by preparing time/intensity curves. It is also possible to obtain information on cardiac morphology, wall motion, and myocardial metabolism in addition to perfusion data by combining myocardial perfusion studies with methods such as high speed cine MRI, tagging, or myocardial MRS. It is possible that this method will also be useful in studying myocardial viability.     

Recent developments in the prognostic use of myocardial perfusion imaging

Stress myocardial perfusion imaging has become a mainstay in the noninvasive assessment of patients with known or suspected coronary artery disease for several compelling reasons. Radionuclide myocardial perfusion imaging can be performed using a variety of stressors, including exercise, pharmacologic stress (including dipyridamole, adenosine, dobutamine, and arbutamine), or a combination of exercise and pharmacologic stress. The combination of exercise and pharmacologic stress allows an assessment of the patient's exercise tolerance, to be performed while adequately stressing him or her pharmacologically. Radiopharmaceutical choice has been expanded to include not only thallium-201 but also technetium-based imaging agents such as sestamibi and tetrofosmin. The use of technetium imaging agents has recently been enhanced by the ability to assess ventricular function using gated single-photon emission computed tomography (SPECT) imaging techniques. Finally, the ability to provide prognostic information in the same patients has led to incremental clinical use.     

Assessing myocardial perfusion in coronary artery disease with magnetic resonance first-pass imaging

MRFP perfusion imaging can now be used clinically on most MR scanner systems (1.0 to 1.5 T). The current experimental data demonstrate that MRFP imaging allows the quantitative assessment of myocardial blood flow changes and accurate measurements of collateral flow, including changes in the collateral dependent zones. Certain protocols, however, as outlined here have to be followed to obtain all the possible diagnostic information. Based on the current data on MRFP imaging, it is realistic to anticipate that MRFP imaging in combination with cine or tagging MR imaging will provide clinicians with better methods to distinguish stunned and hibernating, from nonviable myocardium and obtain better outcome data. Dedicated MR scanners are now being designed to meet the needs for MR imaging of patients with coronary artery disease. These scanners, small in size and with better patient access, make placement near the coronary care unit or catheterization laboratory feasible. This is a major step toward enhancing the utility of this new technique by providing the necessary infrastructure for scanning large numbers of patients. The main obstacle to wider use of these new diagnostic tools to assess perfusion is the lack of a large clinical database because there have not yet been major multicenter trials. With the development of novel intravascular contrast agents, however, larger trials are planned that should provide the clinical data mandatory for full integration of MRFP imaging into clinical practice. In particular, the development of dedicated and user-friendly perfusion analysis software will create the means to evaluate MR perfusion data accurately in large patient populations. These studies need to be conducted in a collaborative fashion by cardiologists, heart surgeons, and radiologists to be fully accepted by health care providers in an increasingly cost-averse and competitive health care environment.     

Prognostic value of vasodilator myocardial perfusion imaging in patients with left bundle-branch block

BACKGROUND: The prognostic value of tomographic myocardial perfusion imaging with dipyridamole or adenosine in patients with left bundle-branch block has not been established. METHODS AND RESULTS: The study group consisted of 245 patients with left bundle-branch block who underwent tomographic (single photon emission tomography) myocardial perfusion imaging with thallium-201 (n=173) or technetium-99m sestamibi (n=72) and either dipyridamole (n=153) or adenosine (n=92) stress. Patients were prospectively classified into two groups. Patients were classified as "high risk" if they had (1) a large severe fixed defect (n=28), (2) a large reversible defect (n=36), or (3) cardiac enlargement and either increased pulmonary uptake (thallium) or a decreased resting ejection fraction (sestamibi) (n=20). The remaining 161 patients (66% of the study group) were at "low risk." Follow-up was 99% complete at 3+/-1.4 years. Three-year overall survival was 57% in the high-risk group compared with 87% in the low-risk group (P<.0001). Survival free of cardiac death/nonfatal myocardial infarction/cardiac transplantation was 55% in the high-risk group and 93% in the low-risk group (P<.0001). The presence of a high-risk scan had significant incremental prognostic value after adjustment for age, sex, diabetes, and previous myocardial infarction (P<.0001). Patients with a low-risk scan had an overall survival that was not significantly different from that of a US age-matched population (P=.86). CONCLUSIONS: Tomographic myocardial perfusion imaging with adenosine or dipyridamole stress provides important prognostic information in patients with left bundle-branch block, which is incremental to clinical assessment.     

Insights into the assessment of myocardial perfusion offered by different cardiac imaging modalities

Myocardial perfusion may be very broadly defined as the tightly regulated nutrient delivery to cardiac tissue. The different components of perfusion are myocardial blood flow, oxygen delivery, myocardial oxygen consumption, and myocardial blood volume. Historically, focus has been placed mostly on the assessment of blood flow. In many instances, knowledge of flow without information about these other aspects is inadequate. This review discusses the various cardiac imaging techniques used for the assessment of myocardial perfusion that represent diverse physiologic measures of "perfusion." Their strengths and limitations are discussed as is their relevance to specific clinicopathologic conditions. Significant work still needs to be performed before all the aspects of myocardial perfusion can be precisely measured in human beings.     

Nitrate-augmented myocardial imaging for assessment of myocardial viability

201Tl myocardial perfusion imaging is presently done by several possible strategies. Stress/delayed redistribution, stress/redistribution/reinjection, and rest/redistribution imaging can be useful in the clinical assessment of myocardial viability. Unfortunately, the extent of myocardial viability may still be underestimated even by 201Tl reinjection imaging, compared with 18F-fluorodeoxyglucose positron emission tomography. 99mTc-labeled sestamibi imaging provides results similar to those of 201Tl imaging in the detection of coronary artery disease, but several previous studies suggest that stress/rest 99mTc-labeled sestamibi imaging significantly underestimates myocardial viability. Recently it has been reported that the administration of nitrates, before 201Tl reinjection, improves detection of defect reversibility. Several studies also suggested that administration of nitrates before the injection of 99mTc-labeled sestamibi significantly improved detection of reversibility with this agent, whereas additional studies showed further that this combination improves the predictive accuracy for recovery of left ventricular function and perfusion after coronary revascularization, compared with a standard rest 99mTc-labeled sestamibi study. Nitrate administration before the injection of 201Tl and 99mTc-labeled sestamibi may thus be a potentially attractive alternative for the evaluation of myocardial viability. Although the available results are encouraging, further studies are needed to evaluate the clinical value of 201Tl and 99mTc-labeled sestamibi imaging, in combination with nitrates, for predicting recovery of left ventricular dysfunction.     

Edge detection in brain SPET perfusion imaging: a comparison of several methods

Four methods of brain edge detection on brain SPET perfusion (99Tcm-hexamethylpropylene amine oxime) images were compared: ellipse adaptation, simple thresholding (four threshold values), a low threshold (40%) followed by 1, 2 or 3 pixel erosion, and the Deriche 3D adaptive cut-off frequency method (four filter widths: alpha = 1, 2, 3 or 4). The SPET data of six patients were reconstructed to obtain 10 axial slices, each 10 mm thick, covering the whole brain. On the 60 axial slices, the methods were compared based on automaticity, computation time and accuracy of edge detection compared with morphological edges drawn manually on the patients' 3D co-registered magnetic resonance imaging (MRI) scans. The proportion of pixels inside the contour defined by the MRI scan but outside the SPET edge (p(i)), and the proportion of pixels inside the contour defined by the SPET image but outside the MRI contour (pe), were calculated. The thresholding methods provided interesting results, particularly the application of a low threshold value (40%), followed by a 2 pixel erosion, which required a computation time of 12 s (p(i) = 5.7 +/- 2.2%; pe = 2.7 +/- 0.9%). Because of adjustments to each slice of the ellipse axis, the processing time of this method was about 3 min (p(i) = 1.5 +/- 1.4%; pe = 11.3 +/- 3.4%). The Deriche 3D filter was time-consuming (6 min for 10 slices on a NXT workstation, SMV International). With this method, the best edge fitting was found with a filter width of 3 and 4 (p(i) = 9.6 +/- 11.1%; pe = 14.1 +/- 23.2%; alpha = 3). Three-dimensional filtering methods must be refined to reduce the computation time and to improve brain edge fitting accuracy when compared with the eroded thresholding method.     

Preliminary evaluation in humans of Tc-99m-Q3, a new tracer for myocardial perfusion imaging

We studied the alterations in binding of cyclic AMP as an indicator of particulate cyclic AMP-dependent protein kinase binding activity following transient cerebral ischemia in Mongolian gerbils and examined the effects of vinconate and pentobarbital against alterations in the binding. Animals were allowed to survive for 5 h and 7 days after 10 min of cerebral ischemia induced by bilateral occlusion of common carotid arteries. [3H]Cyclic AMP binding was significantly reduced in the hippocampus 5 h after ischemia, whereas the striatum showed no significant change in the binding. Seven days after ischemia, a severe reduction of [3H]cyclic AMP binding was noted in the dorsolateral striatum, hippocampal CA1 and CA3 sectors, and dentate gyrus. Intraperitoneal administration of vinconate (100 or 300 mg/kg) showed a significant elevation of [3H]cyclic AMP binding in the striatum, stratum pyramidale of hippocampal CA1 and CA3 sectors, and dentate gyrus 5 h after ischemia. By contrast, the intraperitoneal administration of pentobarbital (40 mg/kg) showed no significant alteration of [3H]cyclic AMP binding in most of these regions. However, vinconate and pentobarbital prevented a significant reduction of [3H]cyclic AMP binding in the dorsolateral striatum and stratum pyramidale of hippocampal CA3 sector 7 days after ischemia, although both drugs failed to prevent damage to the hippocampal CA1 sector. These results suggest that alteration in cyclic AMP binding may not be a major factor in causing ischemic neuronal damage.     

Ventilation and perfusion imaging by electrical impedance tomography: a comparison with radionuclide scanning

Cytokine gene transfer into tumor cells has been shown to mediate tumor regression and antimetastatic effects in several animal models via immunomodulation. Therefore, clinical protocols have been developed to treat cancer patients with cytokine gene-modified tumor cells. We inserted the genes coding for the p35 and p40 chain of interleukin-12 (IL-12) in two independent eukaryotic expression vectors and transduced melanoma cells of 15 different primary tumor cultures with both plasmids by a ballistic gene transfer approach. Secreted IL-12 demonstrated strong bioactivity by inducing interferon-gamma release from peripheral blood lymphocytes upon coculture with cell culture supernatants after IL-12 gene transfer which could at least partly be blocked by IL-12-specific antisera. Further enrichment of transduced tumor cells by magnetic separation directly after gene transfer increased cytokine secretion from a mean of 119 pg in the unsorted to 507 pg IL-12 (24 h/10(8) cells) in the magnetically enriched cell fraction. Irradiation of these cells led to a further elevation of secreted IL-12 (mean 987 pg). Elevated IL-12 levels were detected over 7 days after irradiation in vitro. In a subsequent first clinical phase I study six patients with metastatic melanoma were vaccinated with autologous, interleukin-12 gene-modified tumor cells. Melanoma cells were expanded in vitro from surgically removed metastases, transduced by ballistic gene transfer, irradiated and were then injected subcutaneously (s.c.) at weekly intervals. Clinically, there was no major toxicity except for mild fever. All patients completed more than four s.c. vaccinations over 6 weeks and were eligible for immunological evaluation. Post-vaccination, peripheral mononuclear cells were found to contain an increased number of tumor-reactive proliferative as well as cytolytic cells as determined by a limiting dilution analysis in two patients. Two patients developed DTH reactivity against autologous melanoma cells and one had a minor clinical response. Biopsies taken from that patient's metastases revealed a heavy infiltration of CD4+ and CD8+ T lymphocytes. In conclusion, vaccination induced immunological changes even in a group of advanced, terminally ill patients. These changes can be interpreted as an increased antitumor immune response.     

A comparison of SPECT and planar ventilation perfusion lung scanning

In order to define the role of Single Photon Emission Computed Tomography (SPECT) in the diagnosis of pulmonary embolus; SPECT and Planar ventilation and perfusion lung studies were performed consecutively on eleven patients referred with suspected embolus. Three patients were shown to have 'high probability' ventilation perfusion mismatches. SPECT imaging allowed segmental localisation of the perfusion defect and revealed additional defects not seen on planar scans. SPECT lung study was performed with minimal technical difficulty and was well tolerated by all patients studied. SPECT is likely to become the method of choice for investigating patients referred with suspected pulmonary embolus.