Edward J. Hoffman

Quantitation in positron emission computed tomography: 1. Effect of object size.

The effect of object size on the capability of positron emission computed tomography to measure isotope concentrations in a cross section was studied. The relationship between the apparent isotope concentration in an image and the true concentration was measured as a function of object size for three instrument resolutions and four convolution filters. The relationship between image size and object size was also measured under the same conditions. Depression of apparent isotope concentration in an image for objects equal in size to the instrument resolution (FWHM) was significant (50% for a cylinder and 25% for a bar). For objects larger than 1.0 FWHM, accurate object sizes can be estimated from the images. Thus, reasonably accurate and practical schemes of compensation for object size effects can be implemented for objects larger than 1.0 FWHM. Accuracy in quantitating isotope concentrations in smaller objects is seriously compromised by the loss of sensitivity to the object size and the large correction factors required to compensate for instrument response. The results of the measurements were found to be in good agreement with theoretical predictions for ideal systems of comparable resolution.

Measuring PET scanner sensitivity: relating countrates to image signal-to-noise ratios using noise equivalents counts

True coincidence count (TCC) and noise equivalent count (NEC) curves were measured with a standardized 20-cm-diameter nylon cylinder for five different CTI/Siemens PET (positron emission tomography) scanners with several scanner-collimator combinations: (1) 831/08-12 with 1-mm collimator septa; (2) 933/08-12 and 933/08-16 with 3 to 1-mm tapered collimator septa; and (3) 931/08-12 with 3 to 1-mm tapered and a 1-mm collimator septa and the 931/08-16 with 3 to 1-mm tapered collimator septa. In addition, TCC and NEC curves on the 933/08-12 were compared with those from an Alderson brain phantom. In general, it is found that the TCC curves indicated peak count rates and activity levels that were as much as 50% higher than the corresponding values from NEC curves. The primary factor causing this difference is the noise effect of the randoms component. It is demonstrated that, compared to the Alderson brain phantom, the standard 20-cm cylinder is a poor predictor of count rate performance for PET brain imaging. >

Calculation of positron range and its effect on the fundamental limit of positron emission tomography system spatial resolution.

Developments in positron emission tomography (PET) technology have resulted in systems with finer detector elements designed to further improve spatial resolution. However, there is a limit to what extent reducing detector element size will improve spatial resolution in PET. The spatial resolution of PET imaging is limited by several other factors, such as annihilation photon non-collinearity, positron range, off-axis detector penetration, detector Compton scatter, undersampling of the signal in the linear or angular directions for the image reconstruction process, and patient motion. The overall spatial resolution of the systems is a convolution of these components. Of these other factors that contribute to resolution broadening, perhaps the most uncertain, poorly understood, and, for certain isotopes, the most dominant effect is from positron range. To study this latter effect we have developed a Monte Carlo simulation code that models positron trajectories and calculates the distribution of the end point coordinates in water for the most common PET isotopes used: 18F, 13N, 11C and 15O. In this work we present some results from these positron trajectory studies and calculate what effect positron range has on the overall PET system spatial resolution, and how this influences the choice of PET system design parameters such as detector element size and system diameter. We found that the fundamental PET system spatial resolution limit set from detector size, photon non-collinearity and positron range alone varied from nearly 1 mm FWHM (2 mm FWTM) for a 10-20 cm diameter system typical for animal studies with 18F to roughly 4 mm FWHM (7 mm FWTM) for an 80 cm diameter system typical for human imaging using 15O.

3-D phantom to simulate cerebral blood flow and metabolic images for PET

A three-dimensional brain phantom has been developed to simulate the activity distributions found in the human brain in the cerebral blood flow and metabolism studies employed in PET (positron emission tomography). The phantom has a single contiguous chamber and utilizes thin layers of lucite to provide apparent relative concentrations of 5, 1, and 0 for grey matter, white matter, and ventricles, respectively, in the brain. The phantom and an ideal image set were created from the same set of data. Thus, the user has a basis for comparing measured images with an ideal image set, which enables the user to make quantitative evaluation of the errors in PET studies with a data set similar to that obtained in patient studies. >

Noninvasive assessment of coronary stenoses with myocardial perfusion imaging during pharmacologic coronary vasodilatation. V. Detection of 47 percent diameter coronary stenosis with intravenous nitrogen-13 ammonia and emission-computed tomography in intact dogs.

To determine the minimal coronary lesions detectable with perfusion imaging, 16 stenoses of 43 to 66 percent diameter narrowing were applied to the left circumflex coronary artery of three chronically instrumented intact dogs. Orthogonal diastolic coronary arteriograms, obtained on cut film by triggering X-ray exposures from the electrocardiogram while injecting contrast medium through a chronically implanted coronary arterial catheter, were analyzed quantitatively by computer. Fifteen millicuries of nitrogen-13 ammonia was injected intravenously during resting conditions, and emission-computed tomography was performed without electrocardiographic gating. One hour later, after residual nitrogen-13 ammonia had decayed, 15 mg of intravenous dipyridamole was given followed by a second dose of intravenous nitrogen-13 ammonia and repeat performance of emission-computed tomography. The cross-sectional tomographs of the heart were of high quality and revealed in the images obtained with dipyridamole definite perfusion defects with coronary stenoses of 47 percent or greater diameter narrowing. Stenoses of 45 percent diameter narrowing or less did not produce perfusion defects. Quantitative perfusion abnormalities approximated the quantitative severity of stenoses. It is concluded that noninvasive myocardial emission-computed tomography with nitrogen-13 ammonia during dipyridamole-induced coronary vasodilatation detects mild coronary stenoses for purposes of potential medical intervention.

13N ammonia myocardial imaging at rest and with exercise in normal volunteers. Quantification of absolute myocardial perfusion with dynamic positron emission tomography.

Positron emission tomography (PET) was applied to the measurement of myocardial perfusion using the perfusion tracer 13N-labeled ammonia. 13N ammonia was delivered intravenously to 13 healthy volunteers both at rest and during supine bicycle exercise. Dynamic PET imaging was obtained in three cross-sectional planes for 10 minutes commencing with each injection. The left ventricle was divided into eight sectors, and a small region of interest was assigned to the left ventricular blood pool to obtain the arterial input function. The net extraction of 13N ammonia was obtained for each sector by dividing the tissue 13N concentration at 10 minutes by the integral of the input function from the time of injection to 10 minutes. With this approach for calculating net extractions, rest and exercise net extractions were not significantly different from each other. To obviate possible overestimation of the true 13N ammonia input function by contamination by 13N-labeled compounds other than 13N ammonia or by spillover from myocardium into blood pool, the net extractions were calculated using only the first 90 seconds of the blood and tissue time-activity curves. This approach for calculating net extractions yielded significant differences between rest and exercise, with an average ratio of exercise to rest of 1.38 +/- 0.34. Nonetheless, the increase was less than predicted from the average 2.7-2.8-fold increase in double product at peak exercise or the 1.7-fold increase in double product at 1 minute after exercise. However, when the first 90 seconds of dynamic data were fit with a two compartment tracer kinetic model, average perfusion rates of 0.75 +/- 0.43 ml/min/g at rest and 1.50 +/- 0.74 ml/min/g with exercise were obtained. This average increase in perfusion of 2.2-fold corresponded to similar average increases in double product. Thus, the noninvasive technique of PET imaging with 13N ammonia shows promise for future applications in determining absolute flows in patients with coronary artery disease.

ECAT: a new computerized tomographic imaging system for positron-emitting radiopharmaceuticals

The ECAT was designed and developed as a positron imaging system capable of providing high contrast, high resolution, quantitative images in two-dimensional (2-D) and tomographic formats. The flexibility in its variety of imaging problems. High (HR), medium (MR), and low (LR) tomographic resolutions are 0.95 +/- 0.1, 1.3 +/- 0.1, and 1.7 +/- 0.1 cm FWHM; high, medium, and low resolutions in 2-D images are 0.85 +/- 0.1, 1.3 +/- 0.1 and 1.7 +/- 0.1, depending on resolution mode employed. ECT system efficiency is 30,100, 15,900, and 9,200 c/sec/muCi/cc with a 20-cm diameter phantom at LR, MR, and HR. Because of the geometric, detector, electronic and shielding design of the system, count-rate capability and linearity are high, with minimum detection of scattered radiation and random coincidence. Measured error agrees well with theoretical statistical predictions down to a level of 1.4% standard deviation. The redundant sampling scheme of this system significantly reduces errors caused by motion and detector instability. Scan times are variable from 10 sec to several min/slice and multiple levels are automatically performed by computer control of patient bed. A variety of human studies illustrate image quality, resolution, and efficiency of both ECT and 2-D imaging mode. Examples of the noninvasive study method have been made possible through development of ECT.

Cancer detection with whole-body PET using 2-[18F]fluoro-2-deoxy-D-glucose.

Objective This study was done to determine the feasibility and potential utility of whole-body PET using the glucose analogue 2-[18F]fluoro-2-deoxy-D-glucose (FDG) for the detection of primary malignancies and metastatic lesions. Materials and Methods This was a prospective, nonrandomized study of whole-body FDG-PET imaging carried out at a large university teaching hospital in Los Angeles, CA, U.S.A. The study group consisted of all patients referred for PET imaging (87) with a suspected diagnosis of primary or recurrent malignancy and who had eventual histological confirmation of their lesions. Results In the 87 patients, whole-body PET studies were positive (presence of focal FDG uptake relative to surrounding tissues uptake) in 61 of 70 patients (87%) with subsequent biopsy-confirmed primary or recurrent malignant lesions, including carcinomas of breast, lung, ovary, prostate, colon, urinary bladder, and gallbladder origin, as well as malignant melanoma, carcinoid, osteosarcoma, lymphoma, and spinal cord astrocytoma. The PET images revealed no focal hypermetabolism at the known site of tumor in patients with primary prostate carcinoma (two), microscopic ovarian carcinoma (two), breast carcinoma (one), low-grade carcinoid tumors (two), and one patient with recurrent microscopic osteogenic sarcoma. The PET studies detected the primary lesion in 15 of 17 patients with breast carcinoma and in 6 of 6 patients with primary lung carcinoma. Of the 17 patients with benign biopsies, 13 patients had FDG-PET studies without focal areas of uptake. Conclusion Because of the high glycolytic rate of malignant tissue, the whole-body FDG-PET technique has promise in the detection of a wide variety of both primary and metastatic malignancies. The presence of FDG uptake in benign inflammatory conditions may limit the specificity of the technique. The sensitivity for the detection of malignant lesions was 87% and the positive predictive value was 94%. The whole-body FDG-PET method is promising both in determining the nature of a localized lesion and in defining the systemic extent of malignant disease.

Quantitation in Positron Emission Computed Tomography: 2. Effects of Inaccurate Attenuation Correction

Effects of inaccurate attenuation correction on quantitation in positron emission computed tomography were investigated by both computer simulation and theoretical analysis, followed by experimental verification with phantom measurements. It was found that, due to the finite width of detector responses, compensation of scan measurements by measured attenuation correction factors does not completely correct for attenuation. For FWHM greater than 1.8 cm, errors in object size and in activity levels of reconstructed images are more than 4%. Mismatches between true and assumed attenuation media are found to give large errors. These mismatches include object shift, incorrect size and shape, uniform and nonuniform mismatches in attenuation coefficients, and nonzero background levels. Errors as large as 14% in the reconstructed activity level can be introduced by a 5 mm shift in object position. A 5% error in the cylinder diameter can give differences between the total reconstructed activity and true value more than 12%. Strong image distortions, which could lead to incorrect interpretations of images are created by object shift and by nonuniform mismatches in attenuation coefficient. It was also found that statistical noise in measured attenuation correction factors can significantly increase noise levels in images, resulting in lower effective total counts for the emission scan. Effective total counts can be estimated as Neff = kNxmNem/(Nem + kNxm), where Nem and Nxm are total counts in emission and transmission scans, and k is a scanner dependent factor, which accounts for configuration differences.

Intramural myocardial shortening in hypertensive left ventricular hypertrophy with normal pump function.

BACKGROUND In hypertensive left ventricular hypertrophy (LVH), intrinsic myocardial systolic function may be normal or depressed. Magnetic resonance tagging can depict intramural myocardial shortening in vivo. METHODS AND RESULTS Tagged left ventricular magnetic resonance images were obtained in 30 hypertensive subjects with LVH (mean LV mass index, 142 +/- 41 g/m) and normal ejection fraction (mean, 64 +/- 9%) using spatial modulation of magnetization. In 26 subjects, circumferential myocardial shortening (%S) was compared with results obtained in 10 normal subjects at endocardium, midwall, and epicardium on up to 4 short-axis slices each. Similarly, in 10 subjects, midwall long-axis shortening at basal, midventricular, and apical sites was compared with results obtained in 12 normal volunteers. Circumferential %S was reduced in hypertensive subjects. Mean shortening was 29 +/- 6% at the endocardium in hypertensive subjects versus 44 +/- 6% in normal subjects (P = .0001); 20 +/- 6% at the midwall versus 30 +/- 6% (P = .0001); and 13 +/- 5% at the epicardium versus 21 +/- 5% (P = .0002). However, the transmural gradient in percent shortening from endocardium to epicardium in hypertensive subjects paralleled that in normal subjects. The normal base-to-apex gradient in circumferential %S was absent in LVH. In contrast to normal subjects, circumferential %S showed regional heterogeneity in hypertensive subjects, being maximal in the lateral wall and least in the inferior wall. Longitudinal shortening was also uniformly depressed in hypertensive subjects: 10 +/- 9% at the base versus 21 +/- 6% in normal subjects (P = .0001); 14 +/- 8% at the midventricle versus 18 +/- 3% (P = .03); and 14 +/- 8% at the apex versus 18 +/- 4% (P = .04). CONCLUSIONS In hypertensive LVH with normal pump function, intramural circumferential and longitudinal myocardial shortening are depressed.