Regional Tracer Distribution Research Articles

ACCELERATED TRACER WASHOUT IN REGIONS OF SYMPATHETIC DENERVATION IN HEART FAILURE PATIENTS WITH ISCHEMIC CARDIOMYOPATHY USING FLUBROBENGUANE POSITRON EMISSION TOMOGRAPHY IMAGING

<h3>BACKGROUND</h3> Sympathetic denervation has been shown to predict the risk of sudden cardiac death in ischemic cardiomyopathy (ICM) heart failure patients with implanted cardiac defibrillators. The previous PAREPET trial (JACC 2014;63(2):141) used the PET tracer hydroxyephedrine (HED) which is a false neurotransmitter analog of norepinephrine. This established tracer is labeled with the short-lived isotope C-11, which limits its widespread utility for risk stratification in clinical practice. The purpose of this study was to evaluate the ability of a new F-18-labeled PET tracer LMI-1195 (flubrobenguane) to measure regional denervation (tracer uptake) as well as sympathetic tone (washout rate) in ICM patients with heart failure. <h3>METHODS AND RESULTS</h3> A subset of patients (N=7) in the LMI-1195 vs HED validation trial underwent early (30 min) and late (4 hours) PET-CT imaging following injection of 3 MBq/kg of flubrobenguane. Five subjects were ICM patients and 2 were healthy normal controls. Regional tracer distribution was quantified on the early and late uptake images using the clinical 4DM-PET analysis program (Ann Arbor, MI). Percent washout rate was measured as (early-late) / early uptake (x100%) using a 9-segment model of left ventricle. In normal controls, there was minimal washout over the 4-hour interval between early and late images (4 +/- 4%). Tracer washout was significantly accelerated (P < 0.0001) in both ischemic regions and in remote (perfused) regions in the ICM patients (21 +/- 10% and 17% +/- 9% respectively), suggesting increased sympathetic tone in the whole-LV of these heart failure patients, with regionally higher tone in the ischemic zone. <h3>CONCLUSION</h3> Initial pilot studies evaluating the novel PET tracer [18F]flubrobenguane as a marker of presynaptic neuronal function in humans with and without HF was performed, showing accelerated washout in regions of sympathetic denervation in patients with ischemic cardiomyopathy. If confirmed in larger studies, this would represent a novel and non-invasive method to quantify cardiac sympathetic activity in-vivo. This new imaging method may be helpful in the future to identify cardiac regions associated with elevated arrhythmogenic risk.

Impact of tissue photon attenuation in small animal cardiac PET imaging

ObjectivesTissue photon attenuation is one of the essential artifacts requiring correction in clinical cardiac positron emission tomography (PET) imaging. However, due to small body size its impact on diagnostic accuracy in small rodents is considered to be limited or even ignorable. The present cardiac PET study compares lean and obese rats to determine the influence of tissue attenuation on quantitative assessment as well as regional tracer distribution. MethodsA dedicated small animal PET system equipped with a 57Co rotating source for transmission was used. To assess the impact of tissue attenuation in rats with different body sizes, cardiac 18F­FDG -PET studies for Zucker diabetic fatty rats (obese rats) and Zucker lean rats (lean rats) were performed. The radiotracer activity reduction by attenuation was compared between the two groups. Regional tracer distribution calculated with and without attenuation correction was also assessed. ResultsThe chest diameter was significantly longer in obese than in lean rats (5.6±0.3cm in obese and 4.5±0.2cm in lean rats, p<0.0001). Whereas the activity reduction by attenuation was significantly greater in obese than in lean rats (44.1±2.5% and 5.1±3.1%, p<0.0001), the regional variation of tissue attenuation among the ventricular walls was minimal in both lean (p=0.73) and obese rats (p=0.65). ConclusionAttenuation correction is indispensable for accurate comparison of cardiac tracer activity between animals with different body size, whereas it can be omitted for evaluation of regional tracer distribution.

P-glycoprotein Function in the Rodent Brain Displays a Daily Rhythm, a Quantitative In Vivo PET Study.

The blood-brain barrier (BBB) contributes to brain homeostasis by protecting the brain from harmful compounds. P-glycoprotein (P-gp) is one of the major efflux transporters at the BBB. In the present study, we assessed whether (1) P-gp function in the brain is constant or fluctuates across the day and (2) if it is affected by sleep deprivation. Four groups of rats were PET scanned with a radiolabeled P-gp substrate [18F]MC225, each at a different moment of the 12-h light-dark cycle to study diurnal variations: early sleep phase (ZT3), late sleep phase (ZT9), early active phase (ZT15), and late active phase (ZT21). In two additional groups, controls were allowed to sleep normally while experimental animals were sleep-deprived for 10h in a slowly rotating drum during the sleep phase. Kinetic modeling with a one-tissue compartment model fit resulted for all brain regions in 1.2-1.8-fold higher distribution volumes (V T ) at ZT15 than at other time points. V T -values at ZT3, ZT9, and ZT21 were not significantly different from each other. Regional tracer distribution volumes in controls and sleep-deprived animals were also not significantly different. Our results indicate that P-gp function in rats displays a daily rhythm with reduced function at the beginning of the active phase. This rhythm is not dependent on sleep since acute sleep deprivation had no effect. Knowing the diurnal variation of P-gp function could be important for the design of PET studies and for choosing the correct administration time for P-gp-dependent drugs.

Deep brain stimulation of the periaqueductal gray releases endogenous opioids in humans

Deep brain stimulation (DBS) of the periaqueductal gray (PAG) is used in the treatment of severe refractory neuropathic pain. We tested the hypothesis that DBS releases endogenous opioids to exert its analgesic effect using [11C]diprenorphine (DPN) positron emission tomography (PET). Patients with de-afferentation pain (phantom limb pain or Anaesthesia Dolorosa (n=5)) who obtained long-lasting analgesic benefit from DBS were recruited. [11C]DPN and [15O]water PET scanning was performed in consecutive sessions; first without, and then with PAG stimulation. The regional cerebral tracer distribution and kinetics were quantified for the whole brain and brainstem. Analysis was performed on a voxel-wise basis using statistical parametric mapping (SPM) and also within brainstem regions of interest and correlated to the DBS-induced improvement in pain score and mood. Brain-wide analysis identified a single cluster of reduced [11C]DPN binding (15.5% reduction) in the caudal, dorsal PAG following DBS from effective electrodes located in rostral dorsal/lateral PAG. There was no evidence for an accompanying focal change in blood flow within the PAG. No correlation was found between the change in PAG [11C]DPN binding and the analgesic effect or the effect on mood (POMSSV) of DBS. The analgesic effect of DBS in these subjects was not altered by systemic administration of the opioid antagonist naloxone (400ug). These findings indicate that DBS of the PAG does indeed release endogenous opioid peptides focally within the midbrain of these neuropathic pain patients but we are unable to further resolve the question of whether this release is responsible for the observed analgesic benefit.

Novel Approach to Repeated Arterial Blood Sampling in Small Animal PET: Application in a Test-Retest Study with the Adenosine A1 Receptor Ligand [(11)C]MPDX.

PurposeSmall animal positron emission tomography (PET) can be used to detect small changes in neuroreceptor availability. This often requires rapid arterial blood sampling. However, current catheterization procedures do not allow repeated blood sampling. We have developed a procedure which allows arterial sampling on repeated occasions in the same animal.ProceduresEleven male Wistar rats were two times catheterized via a superficial branch of a femoral artery and scanned with [11C]MPDX and blood sampling. PET images were co-registered to a magnetic resonance imaging (MRI) template. Regional tracer distribution volumes (VT) in the brain were calculated by the Logan analysis. The procedure was repeated after 1 week.ResultsSurgery was successful in 90 % of the cases, and discomfort was minor. The VT data showed small differences between test and retest, low between subject variability, and a strong agreement between and within subjects.ConclusionRepeated quantitative imaging with a high reproducibility is possible with this approach.

Understanding the topology of 18F-AV-1451 (also known as T807) PET tau images in Alzheimer’s disease

18F-AV-1451 is a PET tracer in development for assessment of neurofibrillary tau pathology. Understanding the relationship of tau pathology in Alzheimer's Disease (AD) to disease stage or exploring longitudinal changes in 18F-AV-1451 uptake may require quantitation of various aspects of tracer distribution including amplitude, extent and laterality of regional tracer distribution. PET scans were acquired 80-100 min post injection of 18F-AV-1451 in 154 subjects: 14 young healthy controls (YCN), 34 healthy older controls (OCN), 72 with mild cognitive impairment (MCI) and 34 with diagnosis of AD. Florbetapir PET was obtained to establish amyloid positivity (Aβ+). 18F-AV-1451 SUV ratios (SUVr) were calculated on a voxel-wise basis and for AAL regions across neocortical and mesial temporal lobe regions. Voxel-wise methods employed intensity-, extent- and laterality-based metrics. Regional and voxel-wise quantitative measures from PET images were evaluated across diagnostic group and amyloid status (Aβ+/-). Finally, SUVr images were entered into a multi-block barycentric discriminant analysis (MUBADA) to identify regions showing maximal diagnostic group discrimination (OCN, MCI AD and Aβ+ vs. Aβ- subgroups). Analyses showed mean differences between diagnostic groups for all approaches. Effect size (Cohen's D) for distinguishing cohorts was generally greater for extent than intensity metrics (e.g., ∼2.5 for extent metrics and ∼1.8 for intensity for distinguishing impairment). Asymmetry of tracer distribution (left > right) was common and more pronounced in MCI than in AD. MUBADA identified 2 dimensions, with the first of these characterized by increased retention in posterior neocortex (accounting for > 95% of the variance in regional SUVr pattern) and differentiated Aβ+ MCI and AD relative to all other groups. Regional and composite analyses were effective in discriminating cohorts divided by cognitive impairment severity and amyloid positivity. Voxel-based analyses appeared to provide further sensitivity to patterns of laterality and extent of involvement. Future studies will evaluate which methods are most sensitive to change over time. Extent and Intensity Metrics separate groups; laterality indices indicate left- dominant tracer uptake; voxels wise correlations demonstrate regional relationships to cognitive function, and discriminant analyses identify regions predominantly associated with distinguishing Aβ+ AD and MCI subieets from other cohorts.

Discrepant uptake of the radiolabeled norepinephrine analogues hydroxyephedrine (HED) and metaiodobenzylguanidine (MIBG) in rat hearts

(11)C-Hydroxyephedrine (HED) and radioiodinated metaiodobenzylguanidine ((123)I/(131)I-MIBG) are catecholamine analogue tracers for sympathetic nerve positron emission tomography/single photon emission computed tomography (PET/SPECT) imaging. In contrast to humans, rat hearts demonstrate high nonneural catecholamine uptake-2 in addition to neural uptake-1, the contributions of which to tracer accumulation are not fully elucidated. Wistar rats were studied using the following pretreatments: uptake-1 blockade with desipramine 2 mg/kg IV, both uptake-1 and -2 blockade with phenoxybenzamine 50 mg/kg IV, or control with saline IV. HED or (123)I-MIBG was injected 10 min after pretreatment, and rats were sacrificed 10 min later. Heart to blood tissue count ratio (H/B ratio) was obtained using a gamma counter. To determine regional tracer uptake, dual-tracer autoradiography was performed with HED and (131)I-MIBG in Wistar rats with chronic infarction by transient coronary occlusion and reperfusion and in healthy control rats. Local tracer distributions were analyzed, and the infarcted rats' local tracer distributions were compared with histology. The H/B ratios in control hearts were 34.4 ± 1.7 and 25.5 ± 2.1 for HED and (123)I-MIBG, respectively. Desipramine led to a significant decrease in HED (3.2 ± 0.5, p < 0.0001), while there was no change in (123)I-MIBG (25.5 ± 6.4, p = n.s.). Phenoxybenzamine led to a significant decrease in both HED and (123)I-MIBG (3.5 ± 0.02, 4.3 ± 0.7, p < 0.0001). Only HED showed a subepicardium-subendocardium gradient in healthy control hearts which is consistent with physiological innervation, while (131)I-MIBG was evenly distributed throughout the myocardium. (131)I-MIBG uptake defect closely matched the scar area determined by histology [3.8 ± 2.3% ((131)I-MIBG defect) vs 4.0 ± 2.4% (scar)]. However, the scar area was clearly exceeded by the HED uptake defect (9.1 ± 2.2%, p < 0.001). HED uptake showed high specificity to neural uptake-1 in rat hearts. On the other hand, (123)I/(131)I-MIBG demonstrated distinct characters of regional tracer distribution and uptake mechanism that are compatible with significant contribution of nonneural uptake-2.

Can hypoxia-PET map hypoxic cell density heterogeneity accurately in an animal tumor model at a clinically obtainable image contrast?

Background PET allows non-invasive mapping of tumor hypoxia, but the combination of low resolution, slow tracer adduct-formation and slow clearance of unbound tracer remains problematic. Using a murine tumor with a hypoxic fraction within the clinical range and a tracer post-injection sampling time that results in clinically obtainable tumor-to-reference tissue activity ratios, we have analyzed to what extent inherent limitations actually compromise the validity of PET-generated hypoxia maps. Materials and methods Mice bearing SCCVII tumors were injected with the PET hypoxia-marker fluoroazomycin arabinoside (FAZA), and the immunologically detectable hypoxia marker, pimonidazole. Tumors and reference tissue (muscle, blood) were harvested 0.5, 2 and 4 h after FAZA administration. Tumors were analyzed for global (well counter) and regional (autoradiography) tracer distribution and compared to pimonidazole as visualized using immunofluorescence microscopy. Results Hypoxic fraction as measured by pimonidazole staining ranged from 0.09 to 0.32. FAZA tumor to reference tissue ratios were close to unity 0.5 h post-injection but reached values of 2 and 6 when tracer distribution time was prolonged to 2 and 4 h, respectively. A fine-scale pixel-by-pixel comparison of autoradiograms and immunofluorescence images revealed a clear spatial link between FAZA and pimonidazole-adduct signal intensities at 2 h and later. Furthermore, when using a pixel size that mimics the resolution in PET, an excellent correlation between pixel FAZA mean intensity and density of hypoxic cells was observed already at 2 h post-injection. Conclusions Despite inherent weaknesses, PET-hypoxia imaging is able to generate quantitative tumor maps that accurately reflect the underlying microscopic reality (i.e., hypoxic cell density) in an animal model with a clinical realistic image contrast.

CT-based attenuation correction in 82Rb-myocardial perfusion PET–CT: incidence of misalignment and effect on regional tracer distribution

Misalignment of low-dose-CT used for attenuation correction (AC) may cause artifacts in cardiac-PET-CT. The aim was to evaluate incidence and severity of misalignment and its quantitative effects on regional myocardial (82)Rb-distribution. Rest/dipyridamole (82)Rb-perfusion-PET-CT studies of 92 consecutive patients were analyzed for misalignment. Two different scanning protocols were employed: the first 57 patients had separate CTs for rest and stress PET. The following 35 patients had one CT at rest, used for AC of rest and stress PET. Misalignment was visually scored on a five-point scale (0 = no, 1 = minimal, 2 = mild, 3 = moderate, and 4 = severe). In five representative patients with normal perfusion and low probability of disease, 95 polarmaps were created by shifting CT vs PET prior to reconstruction of attenuation-corrected data sets using dedicated software (three dimensions of space; magnitude of shifts, 5, 10, 14 mm). PET/CT -misalignment was detected in 60% of rest and 67% of stress studies. Alignment for rest was better than that for stress (0.7 +/- 0.7 vs 1.0 +/- 0.9, P = 0.03). Comparison of the two protocols revealed no effect on the alignment of the stress study (1.0 +/- 0.9 vs 1.0 +/- 0.9, P = 0.9). Quantitatively, the largest individual effect of any artificial misalignment was a 25% reduction of relative (82)Rb uptake. With a shift of 1 cm, the largest effect in an individual was a 19% decrease. Anterior wall was most frequently influenced by misalignment, but changes of uptake also occurred in all other segments. Misalignment between CT and PET in cardiac-PET-CT influences regional tracer distribution in multiple segments. Repeated CT imaging after dipyridamole does not improve alignment. These results emphasize the need for strategies to improve coregistration in clinical imaging protocols.

2-(2-[2-Dimethylaminothiazol-5-yl]Ethenyl)-6- (2-[Fluoro]Ethoxy)Benzoxazole: A Novel PET Agent for In Vivo Detection of Dense Amyloid Plaques in Alzheimer's Disease Patients

Extensive deposition of dense amyloid fibrils is a characteristic neuropathologic hallmark in Alzheimer's disease (AD). Noninvasive detection of these molecules is potentially useful for early and precise detection of patients with AD. This study reports a novel compound, 2-(2-[2-dimethylaminothiazol-5-yl]ethenyl)-6-(2-[fluoro]ethoxy)benzoxazole (BF-227), for in vivo detection of dense amyloid deposits using PET. The binding affinity of BF-227 to amyloid-beta (Abeta) fibrils was calculated. The binding property of BF-227 to amyloid plaques was evaluated by neuropathologic staining of AD brain sections. Brain uptake and in vivo binding of BF-227 to Abeta deposits were also evaluated using mice. For clinical evaluation of (11)C-BF-227 as a PET probe, 11 normal (healthy) subjects and 10 patients with AD participated in this study. Dynamic PET images were obtained for 60 min after administration of (11)C-BF-227. The regional standardized uptake value (SUV) and the ratio of regional to cerebellar SUV were calculated as an index of (11)C-BF-227 retention. The regional tracer distribution in AD patients was statistically compared with that of aged normal subjects on a voxel-by-voxel basis. BF-227 displayed high binding affinity to synthetic Abeta1-42 fibrils (K(i) [inhibition constant], 4.3 +/- 1.5 nM). Neuropathologic staining has demonstrated preferential binding of this agent to dense amyloid deposits in AD brain. Moreover, a biodistribution study of this agent revealed excellent brain uptake and specific labeling of amyloid deposits in transgenic mice. The present clinical PET study using (11)C-BF-227 demonstrated the retention of this tracer in cerebral cortices of AD patients but not in those of normal subjects. All AD patients were clearly distinguishable from normal individuals using the temporal SUV ratio. Voxel-by-voxel analysis of PET images revealed that cortical BF-227 retention in AD patients is distributed primarily to the posterior association area of the brain and corresponded well with the preferred site for neuritic plaque depositions containing dense Abeta fibrils. These findings suggest that BF-227 is a promising PET probe for in vivo detection of dense amyloid deposits in AD patients.

Attenuation correction for myocardial perfusion imaging

We investigated the impact of photon attenuation in myocardial perfusion imaging with SPECT and PET in patients with coronary artery disease. In fact, the regional tracer distribution can be quantitatively assessed by polar map analysis if the effects of photon attenuation are accounted for. PET imaging permits accurate measurement of and correction for photon attenuation, whereas results of attenuation correction in SPECT imaging have been inconsistent. We compared photon attenuation in resting perfusion imaging studies with SPECT ((99m)Tc-sestamibi) and PET ((13)N-ammonia) from 21 patients. Transaxial images were reconstructed with and without attenuation correction and reoriented into short axis images. Polar map analysis was utilized to generate regional tracer uptake in six anatomical segments. Average segmental photon attenuation calculated as the ratio of counts in corrected and uncorrected images was 7.2 +/- 1.4 in SPECT and 14.0 +/- 3.1 in PET imaging (p < 0.01). This attenuation factor was significantly related to body mass index for both methods (p < 0.001). While attenuation correction for SPECT imaging did compensate for attenuation effects in the inferior wall (from -15% to +6% vs. PET), relative tracer uptake in the anterior wall in SPECT images was significantly reduced after attenuation correction (from -2% to -18% vs. PET, p < 0.01). Differential effects of attenuation correction for myocardial SPECT perfusion imaging need to be considered when algorithms designed to compensate effects of photon attenuation in SPECT imaging are employed in clinical practice.

Quantitative assessment of the effect of x-ray CT attenuation correction on myocardial perfusion in patients with single vessel coronary artery disease

Background: Attenuation artifacts diminish the diagnostic accuracy of myocardial perfusion imaging (MPI). Little quantitative data exist regarding the effect of x-ray CT based attenuation correction (AC) on regional tracer distribution. The purpose of this study is to quantitatively evaluate the effect of AC on MPI in individual vascular territories. Methods: In this study we selected patients with known single vessel disease who had stress technetium-99m sestamibi SPECT testing with and without AC and cardiac catheterization within 6 months. Coronary stenoses were considered significant if ≥ 70% of the mean luminal diameter. Patients with previous coronary bypass or acute myocardial infarction were excluded. Perfusion stress images were analyzed using automated bulls-eye 20 segment quantitative software. Segments below the 75% maximum threshold were considered abnormal. Specific vascular territories were evaluated. The basal anteroseptum and inferoseptum were excluded due to membranous septum variability. Results: Twenty nine patients were selected (8 LAD, 10LCX, 11RCA). Stress imaging showed more abnormal segments in the non-AC compared to the AC images (mean 13.45 vs. 11.41 p=0.0005). When considering specific vascular territories, there were more false positive segments in the RCA (inferior) territory in the non-AC images in all CAD patients (see table) likely representing diaphragmatic attenuation artifact. Abnormally Perfused Regions During Stress (mean) Patient's known CAD LAD AC/Non-AC LCX AC/Non-AC RCA AC/Non-AC LAD 5.3/4.8 p = NS 1.5/2.0 p = NS 3.6/5.3 p = 0.01 LCX 2.9/2.4 NS 3.2/3.1 NS 3.3/5.0 0.008 RCA 3.2/3.0 NS 2.2/3.3 p = 0.02 3.8/5.7 0.0004 Conclusions: Myocardial perfusion imaging using x-ray CT based attenuation correction is an accurate means of detecting single vessel CAD with improved visualization of the inferior wall and less diaphragmatic artifact compared to non-corrected imaging.

713 Prospective study of 18FDG-PET in patients with cervical lymph node metastases from an unknown primary tumor

PET allows non-invasive mapping of tumor hypoxia, but the combination of low resolution, slow tracer adduct-formation and slow clearance of unbound tracer remains problematic. Using a murine tumor with a hypoxic fraction within the clinical range and a tracer post-injection sampling time that results in clinically obtainable tumor-to-reference tissue activity ratios, we have analyzed to what extent inherent limitations actually compromise the validity of PET-generated hypoxia maps.Mice bearing SCCVII tumors were injected with the PET hypoxia-marker fluoroazomycin arabinoside (FAZA), and the immunologically detectable hypoxia marker, pimonidazole. Tumors and reference tissue (muscle, blood) were harvested 0.5, 2 and 4 h after FAZA administration. Tumors were analyzed for global (well counter) and regional (autoradiography) tracer distribution and compared to pimonidazole as visualized using immunofluorescence microscopy.Hypoxic fraction as measured by pimonidazole staining ranged from 0.09 to 0.32. FAZA tumor to reference tissue ratios were close to unity 0.5 h post-injection but reached values of 2 and 6 when tracer distribution time was prolonged to 2 and 4 h, respectively. A fine-scale pixel-by-pixel comparison of autoradiograms and immunofluorescence images revealed a clear spatial link between FAZA and pimonidazole-adduct signal intensities at 2 h and later. Furthermore, when using a pixel size that mimics the resolution in PET, an excellent correlation between pixel FAZA mean intensity and density of hypoxic cells was observed already at 2 h post-injection.Despite inherent weaknesses, PET-hypoxia imaging is able to generate quantitative tumor maps that accurately reflect the underlying microscopic reality (i.e., hypoxic cell density) in an animal model with a clinical realistic image contrast.

Regional distribution of human cerebral vascular mean transit time measured by positron emission tomography

Cerebral vascular mean transit time (MTT) characterizes the cerebral circulation. MTT has been measured in humans by carotid angiography, x-ray computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). However, regional distribution of MTT has not been investigated in detail. Thus, we investigated regional distribution of normal human MTT. Regional cerebral blood flow (CBF) and cerebral blood volume (CBV) were measured by PET with H 2 15O and 11CO, respectively, in each of 10 normal subjects. MTT was calculated as MTT = CBV/CBF. MTT for cerebral cortical regions was 3.2 to 4.4 s. These values were in accord with MTT measured by carotid angiography, CT, and MRI. Considered regionally, MTT was longest in the temporooccipital cortex, and shorter in the cerebellum, thalamus, and putamen, than in all other regions. These regional differences in MTT that are inversely proportional to cerebral perfusion pressure might relate to regional differences in cerebral vascular tone. Simulation studies showed that errors in CBF and thus MTT caused by regional differences in regional tracer appearance time, distribution volume, and gray–white matter mixing were negligible.

Sestamibi SPECT in the detection of myocardial viability in patients with chronic ischemic left ventricular dysfunction: Comparison between visual and quantitative analysis

Background. Technetium 99m sestamibi cardiac scintigraphy is widely used as a means of predicting myocardial viability in patients with chronic ischemic left ventricular (LV) dysfunction. No data are available comparing the results of visual and quantitative analysis of tomographic imaging in the assessment of myocardial viability. The aim of this study was to directly compare visual and quantitative analysis of resting sestamibi single photon emission computed tomography in the identification of viable myocardium in patients with chronic LV dysfunction. Methods and Results. Sixty-five patients with an earlier myocardial infarction and LV dysfunction that had occurred within 1 week underwent echocardiography and resting sestamibi SPECT. In each patient, regional tracer distribution was visually assessed and quantitatively measured in 13 segments. Regional LV function was evaluated in corresponding segments by means of echocardiography. All patients underwent revascularization, and echocardiography was repeated 12 months later as a means of assessing the recovery of regional LV function. Among all akinetic or dyskinetic revascularized segments, 66 of 112 viable segments (59%) and 85 of 100 nonviable segments (81%) were identified by means of visual analysis. Eighty-two of 112 viable segments (73%; P < .05 vs visual analysis) and 74 of 100 nonviable segments (74%; P = .3 vs visual analysis) were identified by means of quantitative analysis, with a threshold of 55%. Receiver operating characteristic curve areas constructed by using visual and quantitative analyses for the detection of myocardial viability in all 212 akinetic or dyskinetic segments were 0.79 ± 0.04 and 0.81 ± 0.03, respectively ( P = not significant). Overall concordance in the detection of myocardial viability between visual and quantitative analysis was observed in 165 of akinetic or dyskinetic dysfunctional segments (78%), with a κ value of 0.6. Conclusions. The results of this study demonstrate that, in patients with chronic myocardial infarction and LV dysfunction, visual and quantitative analysis of sestamibi tomographic images at rest have similar overall accuracy in predicting the recovery of LV function after coronary revascularization procedures. (J Nucl Cardiol 2000;7:406-13.)

Direct comparison of technetium 99m—sestamibi and technetium 99m—tetrofosmin cardiac single photon emission computed tomography in patients with coronary artery disease

Background. Technetium 99m-labeled sestamibi and tetrofosmin tomography have shown high diagnostic accuracy in the detection of coronary artery disease (CAD) . However, few data are available comparing sestamibi and tetrofosmin imaging in the same patients. The aim of the study was to determine the image quality of the two tracers and to compare the results of exercise sestamibi and tetrofosmin tomography in the same patients. Methods. The results of exercise-rest sestamibi and tetrofosmin myocardial tomography were compared in 32 patients with suspected or known CAD who underwent coronary angiography. Image quality was evaluated subjectively. Regional tracer distribution was visually assessed and quantitatively measured in 22 segments/patient. Results. At coronary angiography, 7 patients had normal coronary vessels, 11 single-vessel, and 14 multivessel CAD (≥50 % luminal stenosis) . Image quality judged visually was comparable with the two tracers. Heart/lung and heart/liver ratios for sestamibi and tetrofosmin were not different. At visual analysis, 68 % of the patients with CAD had abnormal findings with sestamibi and 76% with tetrofosmin ( p = NS) . At quantitative analysis, 92% of the patients with CAD had abnormal findings with sestamibi and 96 % with tetrofosmin ( p = NS) . At both visual and quantitative analyses, sensitivity, specificity, and diagnostic accuracy in the detection of individual stenosed vessels were not different between the two tracers. Moreover, for both tracers sensitivity, specificity, and diagnostic accuracy in the detection of diseased vessels were significantly higher (all p < 0.05) at quantitative compared with visual analysis. Finally, defect size and severity were similar for the two tracers.p ] Conclusions. Exercise-rest sestamibi and tetrofosmin tomography yielded images of comparable quality and provided similar results in the identification of patients with CAD and in the detection of the individual stenosed coronary vessels.

A 360 degree acquisition protocol during TC-99 sestamibi and SPECT improves regional tracer distribution

A 360 degree acquisition protocol during TC-99 sestamibi and SPECT improves regional tracer distribution

Iodine-123-labelled fatty acids for myocardial single-photon emission tomography: current status and future perspectives

Renewed interest in the clinical use of iodine-123-labelled fatty acids is currently primarily focused on the use of iodine-123-labelled 15-(p-iodophenyl)pentadecanoic acid (IPPA) and "modified" fatty acid analogues such as 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) which show delayed myocardial clearance, thus permitting single-photon emission tomographic imaging. Interest in the use of BMIPP and similar agents results from the differences which have often been observed in various types of heart disease between regional myocardial uptake patterns of [123I]BMIPP and flow tracer distribution. Although the physiological basis is not completely understood, differences between regional fatty acid and flow tracer distribution may reflect alterations in important parameters of metabolism which can be useful for patient management or therapy planning. These tracers may also represent unique metabolic probes for correlation of energy substrate metabolism with regional myocardial viability. The two agents currently most widely used clinically are 123I-labelled IPPA and BMIPP. While [123I]IPPA is commercially available as a radiopharmaceutical in Europe (Cygne) and Canada (Nordion), multicenter trials are in progress in the United States as a prelude to approval for broad use. [123I]BMIPP was recently introduced as Cardiodine for commercial distribution in Japan (Nihon Medi-Physics, Inc.). [123I]BMIPP is also being used in clinical studies on an institutional approval basis at several institutions in Europe and the United States. In this review, the development of a variety of radioiodinated fatty acids is discussed. The results of clinical trials with [123I]IPPA and [123I]BMIPP are discussed in detail, as are the future prospects for fatty acid imaging.

Nitrogen-13 ammonia perfusion imaging: Relation to metabolic imaging

PET provides an advanced imaging technology that permits the accurate definition of regional tracer distribution. In combination with N-13 ammonia, PET allows for the sensitive and specific detection of coronary artery disease. Results of several studies indicate the superiority of this approach compared with standard thallium-201 tomographic imaging. In addition, regional blood flow can be accurately measured with N-13 ammonia PET, and this approach can be used in conjunction with pharmacologic stress imaging to quantify regional flow reserve. In combination with metabolic markers, N-13 ammonia is capable of assessing myocardial viability. Furthermore, the N-13 ammonia PET approach may differentiate among various forms of cardiomyopathy. More studies are needed to define the cost-benefit ratio of the N-13 ammonia PET technique for the management of patients with coronary artery disease or cardiomyopathy.

Heterogeneous distribution of a diffusional tracer in the aortic wall of normal and atherosclerotic rabbits.

Tracer distribution as an index of nutritional support across the thoracic and abdominal aortas in rabbits in the presence or absence of atherosclerotic lesions was evaluated using [14C]antipyrine, a metabolically inert, diffusible indicator. Intimal plaques were produced by endothelial balloon denudation of the thoracic aorta and a 1% cholesterol diet. After a steady intravenous infusion of 200 microCi of [14C]antipyrine for 60 seconds, thoracic and abdominal aortas and the heart were excised, and autoradiograms of 20-microns-thick sections were quantified, using microcomputer-aided densitometry. Regional radioactivity and regional diffusional support, as an index of nutritional flow estimated from the timed collections of arterial blood, was 367 and 421 nCi.g-1 (82 and 106 ml.min-1.100 g-1) in thoracic aortic media of the normal and atherosclerotic rabbits, respectively. Radioactivity at the thickened intima was 179 nCi.g-1 (p less than 0.01 versus media). The gruel was noted at a deeper site within the thickened intima, and diffusional support here was 110 nCi.g-1 (p less than 0.01 versus an average radioactivity at the thickened intima). After ligating the intercostal arteries, regional tracer distribution in the media beneath the fibrofatty lesion, but not the plaque-free intima, was reduced to 46%. Thus, in the presence of advanced intimal thickening, the heterogeneous distribution of diffusional flow is prominent across the vessel wall, and abluminal routes are crucial to meet the increased demands of nutritional requirements.