Kenneth Nichols

Single photon-emission computed tomography

The current document is an update of an earlier version of single photon emission tomography (SPECT) guidelines that was developed by the American Society of Nuclear Cardiology. Although that document was only published a few years ago, there have been significant advances in camera technology, imaging protocols, and reconstruction algorithms that prompted the need for a revised document. This publication is designed to provide imaging guidelines for physicians and technologists who are qualified to practice nuclear cardiology. While the information supplied in this document has been carefully reviewed by experts in the field, the document should not be considered medical advice or a professional service. We are cognizant that SPECT technology is evolving rapidly and that these recommendations may need further revision in the near future. Hence, the imaging guidelines described in this publication should not be used in clinical studies until they have been reviewed and approved by qualified physicians and technologists from their own particular institutions. 2. INSTRUMENTATION QUALITY ASSURANCE AND PERFORMANCE

Assessment of left ventricular mechanical dyssynchrony by phase analysis of ECG-gated SPECT myocardial perfusion imaging.

Cardiac resynchronization therapy (CRT) has shown benefits in patients with severe heart failure. However, at least 30% of patients selected for CRT by use of traditional criteria (New York Heart Association class III or IV, depressed left ventricular [LV] ejection fraction, and prolonged QRS duration) do not respond to CRT. Recent studies with tissue Doppler imaging have shown that the presence of LV dyssynchrony is an important predictor of response to CRT. Phase analysis has been developed to allow assessment of LV dyssynchrony by gated single photon emission computed tomography myocardial perfusion imaging. This technique uses Fourier harmonic functions to approximate regional wall thickness changes over the cardiac cycle and to calculate the regional onset-of-mechanical contraction phase. Once the onset-of-mechanical contraction phases are obtained 3-dimensionally over the left ventricle, a phase distribution map is formed that represents the degree of LV dyssynchrony. This technique has been compared with other methods of measuring LV dyssynchrony and shown promising results in clinical evaluations. In this review the phase analysis methodology is described, and its up-to-date validations are summarized.

Preoperative parathyroid scintigraphic lesion localization: accuracy of various types of readings.

PURPOSE To retrospectively compare the accuracy of various parathyroid scintigraphy readings for single-gland disease (SGD) and multigland disease (MGD) in patients with primary hyperparathyroidism, with histologic analysis as the reference standard. MATERIALS AND METHODS Institutional review board approval was obtained for this HIPAA-compliant study. Records of 462 patients with primary hyperparathyroidism who underwent preoperative imaging with a technetium 99m ((99m)Tc) sestamibi and (99m)TcO4- protocol that consisted of early and late pinhole (99m)Tc sestamibi, pinhole thyroid imaging, image subtraction, and single photon emission computed tomography (SPECT) were retrospectively reviewed. An experienced nuclear medicine physician without knowledge of other test results or of the final diagnoses graded images on a scale from 0 (definitely normal) to 4 (definitely abnormal). Early pinhole (99m)Tc sestamibi images, late pinhole (99m)Tc sestamibi images, subtraction images, SPECT images, early and late pinhole (99m)Tc sestamibi images, all planar images, and all images--including SPECT images--were read in seven sessions. Receiver operating characteristic curves were generated for each session and were used to calculate sensitivity, specificity, and accuracy. RESULTS A total of 534 parathyroid lesions were excised. Of the 462 patients, 409 had one lesion, whereas 53 had multiple lesions. Reading all images together was more accurate (89%, P = .001) than was reading early (79%), late (85%), subtraction (86%), and SPECT (83%) images separately; however, it was not significantly more accurate than reading planar images (88%) or early and late images together (87%). Reading all images was significantly less sensitive in the detection of lesions with a median weight of 600 mg or less than in the detection of lesions with a median weight of more than 600 mg (86% vs 94%, P = .004). Per-lesion sensitivity for reading all images was significantly higher for SGD than for MGD (90% vs 66%, P < .001). Sensitivity of reading all images together in the identification of patients with MGD was 62%. CONCLUSION Reviewing early, late, and subtraction pinhole images together with SPECT images maximizes parathyroid lesion detection accuracy. Test sensitivity is adversely affected by decreasing lesion weight and MGD.

In vitro human leukocyte labeling with 64Cu: an intraindividual comparison with 111In-oxine and 18F-FDG☆

UNLABELLED We investigated labeling human leukocytes [white blood cells (WBCs)] in vitro with copper-64 (Cu) comparing labeling efficiency, viability and stability of Cu-WBCs with (111)In-oxine (In) WBCs and (18)F-FDG (FDG) WBCs. METHODS Leukocytes from 10 volunteers were labeled with Cu, In and FDG. Forty milliliters of venous blood was collected and leukocyte separation was performed according to standard methods. In-WBCs and FDG-WBCs were labeled according to published methods. For Cu-WBCs, tropolone initially was used as a single chelating agent. Because of poor intracellular Cu retention (54+/-4% at 3 h and 24+/-5% at 24 h), the fluorinated, membrane-permeable divalent cation chelator quin-MF was added. WBCs were incubated in 5 ml saline containing 100 microl of 1mM quin-MF/AM in 2% dimethyl sulfoxide and 74-185 MBq Cu-tropolone for 45 min at 37 degrees C. Labeling efficiencies; in vitro cellular viabilities at 1, 3 and 24 h; and in vitro stabilities at 1, 2, 3, 4 and 24 h (except FDG-WBCs) were determined. RESULTS Mean Cu-WBCs (87+/-4%) and In-WBCs (86+/-4%) labeling efficiencies were comparable and were significantly higher than FDG-WBCs (60+/-19%, P<.001). Cell viabilities, similar at 1 h, were significantly higher for (64)Cu-WBCs at 3 and 24 h. Intracellular retention of activity was always significantly higher for In-WBCs than for Cu-WBCs and FDG-WBCs. At 24 h, intracellular retention was 88+/-4% for In-WBCs and 79+/-6% for Cu-WBCs. CONCLUSION Cu-WBC labeling efficiency and viability were comparable or superior to In-WBCs and significantly higher than FDG-WBCs. Although significantly more activity eluted from Cu-WBCs than from In-WBCs, Cu-WBC probably is adequate for imaging. These data suggest that further investigation of in vitro copper-64-labeled leukocytes for PET imaging of infection is warranted.

Assessment of cardiac wall motion and ejection fraction with gated PET using N-13 ammonia

Background: Cardiac gating is not routinely used in cardiac positron emission tomography (PET). The aim of this study was to determine the feasibility of assessing regional wall motion, ejection fraction (EF), cardiac volumes, and mass with nitrogen-13 ammonia (N-13 ammonia) at the time of PET myocardial perfusion imaging. Methods: We studied 12 healthy volunteers (mean age, 28 ± 8 years) and 53 patients with documented coronary artery disease (CAD) (mean age, 59 ± 11 years). All subjects received a single administration of approximately 600 MBq (16 mCi) of N-13 ammonia intravenously. A 6-minute dynamic scan was performed for quantitative assessment of myocardial perfusion at rest, followed by a separate, 13-minute static scan acquired in the gated mode (8 equal bins). Gated data was imported into the Emory Toolbox. Wall motion was evaluated by dividing the myocardium into 9 anatomic regions graded semiquantitatively. Results: Healthy volunteers had a normal EF (61 ± 6), end systolic volume (ESV) (37 ± 15 mL), end diastolic volume (EDV) (89 ± 25 mL), and cardiac mass (116 ± 18 g). In contrast, patients with CAD showed reduced EF (32 ± 13%) and increased ESV (129 ± 56 mL), EDV (188 ± 68 mL), and cardiac mass (173 ± 45g) (P < 0.001 for each). In patients with CAD, EF measured by gated PET correlated significantly to independent measurements of EF (P < 0.001). Conclusions: Gating of cardiac perfusion images obtained after administration of N-13 ammonia is feasible and appears to be an accurate means of evaluating regional and global cardiac function. Gating can provide important additional diagnostic and prognostic information.

Validation of Gated Blood-Pool SPECT Regional Left Ventricular Function Measurements

Blood-pool (BP)–gated SPECT should be able to detect regional left ventricular (LV) dysfunction, as the modality is fully 3-dimensional and capable of resolving all cardiac chambers. This study investigates the hypothesis that LV segments that have abnormal regional wall motion (WM) on a cardiac MRI scan also have abnormal BP regional ejection fraction (EF) as computed by fully automated quantitation (AQ) of BP data. Methods: A total of 34 patients evaluated for coronary artery disease who underwent visual assessment of WM by review of BP cines and cardiac MRI evaluations were included in this retrospective investigation. Cardiac MRI values for these patients were compared with an institutional database of cardiac MRI values for an age-matched cohort of 10 healthy volunteers. An AQ algorithm segmented the LV BPs on the BP tomograms and subdivided volumes into 17 subregions. Count-versus-time curves were fit to third-order Fourier series for each LV subvolume to compute regional EFs. For cardiac MRI data, endocardial and epicardial drawings were performed manually for 60° samples of 11–13 short-axis tomograms spanning the entire heart, from which regional WM values were computed and rebinned into 17 conventional LV segments. Results: Global EF ranged from 12% to 75% on AQ and from 14% to 75% on cardiac MRI (Pearson correlation coefficient = 0.95, P < 0.0001). Differences were not significant between BP AQ and cardiac MRI in identifying the 12 patients with a global EF less than 35% (McNemar difference, 3%; P = 1.0) and the 19 patients with an EF less than 50% (difference, 3%; P = 1.0). BP AQ was more accurate than was visual assessment for identifying LV segments with abnormal cardiac MRI WM (receiver-operating-characteristic areas, 88% vs. 80%, P < 0.0001) and was more accurate for the left circumflex than for the left anterior descending coronary artery territories (95% vs. 86%, P = 0.01). Differences were not significant between BP AQ and cardiac MRI WM for discriminating normal from abnormal LV segments (McNemar difference, 3.2%; P = 0.14). Conclusion: AQ BP-gated SPECT assessment of regional and global LV WM agrees with independent cardiac MRI calculations and is superior to visual analysis for detecting regional WM abnormalities.

Value of Two-Dimensional Speckle Tracking and Real Time Three-Dimensional Echocardiography for the Identification of Subclinical Left Ventricular Dysfunction in Patients Referred for Routine Echocardiography

Background: While speckle tracking echocardiography (2DSTE) can be used to study longitudinal, circumferential, and radial function, real time 3D echocardiography (3DE) generates dynamic time–volume curves, offering a wide array of new parameters for characterizing mechanical and volumetric properties of the left ventricle (LV). Our aim was to investigate the merit of these new techniques to separate normal from abnormal echocardiograms as well as to identify subclinical disease in reportedly normal subjects. Methods: Eighty‐one patients (mean age 61 ± 16 years) underwent standard 2D echocardiography (2DE) enhanced by 2DSTE and 3DE. The data included LV volumes and ejection fraction (EF), velocities, strain/strain rate, and peak ejection/filling rates. The patients were divided into Group 1: normal (n = 42) and Group 2: abnormal (n = 39) on the basis of an expert interpretation of the resting 2DE. Results: Global longitudinal strain (%) was 17 ± 4 in Group1 and 14 ± 4 in Group2 (P < 0.002). Strain rates (SR, 1/sec) at peak systole (1.1 ± 0.2 vs 0.9 ± 0.3, P < 0.001) and early diastole (1.3 ± 0.3 vs 0.9 ± 0.3, P < 0.001) were also higher in Group1. Three‐dimensional peak ejection and filling rates (EDV/sec) were significantly higher in Group1 (−2.5 ± 0.4 vs −2.1 ± 0.7, and 1.8 ± 0.2 vs 1.5 ± 0.5, P < 0.002, P < 0.001, respectively). The best discriminatory power for predicting a normal 2DE was systolic SR with a sensitivity of 82% and a specificity of 54% using a cutoff value of 1.09. Interestingly, 19/41 (46%) of Group1 patients had systolic SR < 1.09, suggesting subclinical disease. Conclusions: 2DSTE and 3DE can discriminate between normal and abnormal echocardiograms and have the potential to detect subclinical LV dysfunction.

Comparative performance of gated perfusion SPECT wall thickening, delayed thallium uptake, and F-18 fluorodeoxyglucose SPECT in detecting myocardial viability

To evaluate the comparative abilities of gated single photon emission computed tomography (SPECT) wall thickening, delayed thallium-201 (TI-201) SPECT, and F-18 fluorodeoxyglucose (FDG) SPECT in detecting myocardial viability, 23 patients with previous myocardial infarction and clinically suspected viability were studied. Each patient had at least 1 extensive fixed perfusion defect on rest/stress technetium-99m sestamibi SPECT. A total of 41 major vascular territories had fixed defects. The mean (±1 SD) left ventricular ejection fraction determined from gated perfusion SPECT was 26% ±11%. Wall thickening was assessed in a semiquantitative fashion by the regional increase in myocardial intensity during systole and was considered normal when a ≥20% increase was observed. Tl-201 SPECT was acquired 4 hours after resting tracer injection was administered. Viability was considered present when regional defect Tl-201 count density, determined by quantitative analysis, was <20% greater than that on the resting sestamibi scan. FDG SPECT was performed independently with a 10 mCi F-18 FDG dose after oral glucose loading was performed. A camera equipped with ultrahigh energy collimation was used. Quantitative criteria for viability were the same as for Tl-201. In the 23 patients viability within the fixed sestamibi defects was manifest by preserved wall thickening in 8 patients, delayed Tl-201 uptake in 10 patients, and FDG uptake in 18 patients. Nine major vascular territories with fixed defects were judged viable by wall thickening, 11 by Tl-201 SPECT, and 24 by FDG SPECT (P=.0009). We conclude that FDG SPECT demonstrates more evidence of myocardial viability than either gated sestamibi wall thickening or delayed Tl-201 SPECT.

Sestamibi parathyroid scintigraphy in multigland disease.

PurposeFor sestamibi (MIBI) studies in patients with primary hyperparathyroidism, some investigations found that the test sensitivity is lower in patients with multigland disease (MGD) than in those with single-gland disease (SGD), whereas other investigations reported that the sensitivity of MIBI imaging is similar in MGD and SGD. The objectives of this investigation, therefore, were to determine (a) whether there are differences in the sensitivity and specificity of MIBI imaging for detecting parathyroid lesions in patients with MGD and in patients with SGD, (b) whether there is a relationship between test sensitivity and the number of glands involved, (c) whether there are differences in weight between parathyroid lesions in MGD and SGD, (d) whether there are differences in lesion locations between MGD and SGD, and (e) whether MIBI sensitivity in MGD is related to the number, weight, or location of the lesions. Materials and methodsThis was a retrospective investigation of data for 651 patients with biochemically confirmed primary hyperparathyroidism limited to the neck, who underwent preoperative parathyroid lesion localization using a dual tracer 99mTc-MIBI/99mTcO4− protocol that included early and late planar pinhole 99mTc-MIBI, pinhole thyroid imaging, image subtraction, and single photon emission computed tomography. All patients underwent surgery subsequently. Lesion locations were obtained from operative reports; lesion weights were obtained from pathology reports. One experienced nuclear physician, who had no knowledge of the other test results or the final diagnoses, graded studies on a 5-point scale (0=definitely normal to 4=definitely abnormal) while reading all scintigraphic images simultaneously. ResultsThere were 851 lesions among the 651 patients. One hundred and thirty-one (20%) patients had MGD and 520 (80%) patients had SGD. Among the patients with MGD, 74 had two lesions, 45 had three lesions, and 12 had four lesions. MIBI imaging was significantly less sensitive (61 vs. 97%, P<0.0001) and specific (84 vs. 93%, P<0.0001) for MGD than for SGD. Weights of MGD lesions were significantly lower than those of SGD lesions [median 190 mg (10–14 600 mg) vs. median 500 mg (48–27 000 mg), Wilcoxon P<0.0001]. Lesion weights decreased significantly with increasing lesion number (r=−0.42, P<0.0001). MIBI sensitivity for 249 MGD lesions (65%) was significantly less (P<0.0001) than for 249 weight-matched SGD lesions (94%). For these weight-matched lesions, the test sensitivity decreased progressively with increasing lesion number (r=0.97, P=0.006). The spatial distribution of MGD and SGD lesions was similar (P=0.19), and the sensitivity was not related to lesion location for MGD (P=0.32) or SGD (P=0.11) lesions. ConclusionMIBI is significantly less sensitive and specific for detecting parathyroid lesions in MGD than in SGD. Decreased sensitivity is not explained by lesion weight or location, and further studies of factors affecting MIBI imaging in MGD are warranted.

Pinhole Versus Parallel-Hole Collimators for Parathyroid Imaging: An Intraindividual Comparison

This study was undertaken to determine the effects of collimators on the accuracy of preoperative sestamibi parathyroid imaging of the neck. Methods: Forty-nine patients with primary hyperparathyroidism underwent preoperative 99mTc-sestamibi parathyroid imaging. The protocol included early and late pinhole and parallel-hole imaging. One experienced nuclear physician, without knowledge of other test results or final diagnoses, interpreted studies. For both pinhole and parallel-hole images, focally increased sestamibi accumulation outside the normal tracer biodistribution that persisted or increased in intensity from early to late images was interpreted as positive for a parathyroid lesion. Final diagnoses were operatively confirmed in all patients. Results: Fifty-four parathyroid lesions were resected from the 49 patients. Forty-five patients had single-gland disease. Four patients had multigland disease: 3 had 2 lesions and 1 had 3 lesions. Median lesion weight was 840 mg. Pinhole imaging was significantly more sensitive than parallel-hole imaging (89% vs. 56%; P = 0.0003) for all 54 lesions. Specificity did not significantly differ between pinhole and parallel-hole imaging (93% vs. 96%, P = 0.29). Pinhole imaging was significantly more sensitive than parallel-hole imaging for lesions above (100% vs. 68%, P = 0.003) and below (77% vs. 42%, P = 0.03) the median weight and for single-gland disease (96% vs. 67%, P = 0.001). Pinhole imaging also was more sensitive for multigland disease, although the difference was only marginally significant (55% vs. 0%, P = 0.037). Conclusion: Because sensitivity is significantly higher, sestamibi parathyroid imaging of the neck should be performed with a pinhole collimator.