Evaluation of scatter compensation methods by their effects on parameter estimation from SPECT projections.

Three algorithms for scatter compensation in Tc-99m brain single-photon emission computed tomography (SPECT) were optimized and compared on the basis of the accuracy and precision with which lesion and background activity could be simultaneously estimated. These performance metrics are directly related to the clinically important tasks of activity quantitation and lesion detection, in contrast to measures based solely on the fidelity of image pixel values. The scatter compensation algorithms were (a) the Compton-window (CW) method with a 20% photopeak window, a 92-126 keV scatter window, and an optimized "k-factor," (b) the triple-energy window (TEW) method, with optimized widths of the photopeak window and the abutting scatter window, and (c) a general spectral (GS) method using seventeen 4 keV windows with optimized energy weights. Each method was optimized by minimizing the sum of the mean-squared errors (MSE) of the estimates of lesion and background activity concentrations. The accuracy and precision of activity estimates were then determined for lesions of different size, location, and contrast, as well as for a more complex Bayesian estimation task in which lesion size was also estimated. For the TEW and GS methods, parameters optimized for the estimation task differed significantly from those optimized for global normalized pixel MSE. For optimal estimation, the CW bias of activity estimates was larger and varied more (-2% to 22%) with lesion location and size than that of the other methods. The magnitude of the TEW bias was less than 7% across most conditions, although its precision was worse than that of CW estimates. The GS method performed best, with bias generally less than 4% and the lowest variance; its root-mean square (rms) estimation error was within a few percent of that achievable from primary photons alone. For brain SPECT, estimation performance with an optimized, energy-based, subtractive correction may approach that of an ideal scatter-rejection procedure.

Pediatric applications of pinhole magnification imaging.

Pinhole magnification imaging is an important technique for practitioners of pediatric nuclear medicine. This article reviews basic principles of pinhole magnification imaging and ways for optimizing image acquisition with this technique. Applications to skeletal scintigraphy, scrotal scintigraphy and renal cortical scintigraphy are discussed and illustrated.

Pediatric skeletal scintigraphy: applications of pinhole magnification.

Pinhole magnification scintigraphy is an effective means of evaluating the pediatric skeleton because it provides optimal high-resolution images. This technique is indicated when diagnostic uncertainty persists after high-resolution imaging with parallel hole collimation. Pinhole magnification scintigraphy requires approximately 20 minutes of acquisition time per image and meticulous attention to details such as choice of pinhole insert, collimator positioning, and patient immobilization. However, the technique is superior to planar imaging in demonstrating acute osteomyelitis in bone adjacent to growth centers and epiphyseal involvement that is either primary or the result of local spread of infection. In addition, pinhole imaging has proved highly reliable in the early diagnosis of Legg-Calvé-Perthes disease and is useful in depicting osteonecrosis related to specific causes such as corticosteroid treatment or trauma. Scintigraphic manifestations of femoral head ischemia or infarction and findings indicative of osteomyelitis associated with a hip effusion are well demonstrated with pinhole imaging. This technique also helps characterize osteoid osteomas and may be used intraoperatively to confirm the complete excision of this benign tumor. Finally, pinhole magnification scintigraphy clearly depicts fractures of the femoral neck and allows a high degree of confidence in diagnosing injuries to the small bones of the hands and feet.

A technetium-99m SPECT imaging agent which targets the dopamine transporter in primate brain.

The dopamine transporter (DAT), located presynaptically on dopamine neurons, provides a marker for certain neurological diseases. In particular, the DAT is depleted in Parkinson's disease, and the extent of depletion correlates with the loss of dopamine. Herein we describe the design, synthesis, and biological evaluation of technepine, the first 99mTc-labeled SPECT imaging agent which targets the dopamine transporter in striatum. We have demonstrated that the DAT can accommodate a chelating unit attached to the 8-amine function of a tropane skeleton. Further, we have demonstrated for the first time that a molecule can be designed to carry the radionuclide 99mTc across the blood-brain barrier in sufficient quantity to obtain in vivo images of the striatum in monkeys. This advance will undoubtedly lead to the design of new receptor and transporter-mediated 99mTc agents which can label specific transporter and receptor targets in the central nervous system.

Limitations of dual-photopeak window scatter correction for brain imaging.

UNLABELLED: A method for performing scatter corrections that would directly use the photopeak information and would be straightforward for use in clinical practice would be attractive in SPECT imaging. The dual-photopeak window method may be such a method. It relates the scatter fraction to the ratio of the lower to the total parts of a split-photopeak window. We investigated the use of this scatter correction method on a dedicated brain camera. METHODS: Calibration curves for the Ceraspect, a dedicated brain imaging camera, were obtained for four split-window combinations using point sources in air and water. Simulations of the Ceraspect calibration curves at several energy resolution values were obtained using a Monte Carlo simulation of the instrument. RESULTS: The calibration curves, experimental and simulated, revealed an ambiguous and unstable relationship between lower-to-total ratio and scatter fraction. CONCLUSION: The unsatisfactory calibration curves can be attributed to the limited scatter produced in a brain-sized phantom during the calibration process and inherent stability problems in the calibration process. The dual-photopeak window method is not usable for small-field imaging systems and may even be unstable for larger-field systems.

Intratumoral administration of 5-[123I]iodo-2'-deoxyuridine in a patient with a brain tumor.

UNLABELLED: We have initiated a study in which patients suspected of having primary gliomas are given a single intracerebral injection of the thymidine analog 5-[123I]iodo-2'-deoxyuridine ([123I]IUdR). The purpose of the study is to determine the biodistribution of the radiopharmaceutical and to calculate dose estimates to the tumor and normal tissues. METHODS: A patient with a cystic glioma was injected with [123I]IUdR. Whole-body scans and brain scans were obtained at various times after injection, and blood, urine and stools were collected and assayed for radioactivity to assess its biodistribution and clearance. RESULTS: Scintigraphic imaging demonstrated that the distribution of radiolabeled IUdR was mainly confined to the tumor (injection site), stomach and bladder. Disappearance from the tumor site and blood clearance were delayed probably due to collection in the cystic lesion. Eighty percent of the injected dose was recovered in the urine. CONCLUSION: The pharmacokinetics of [123I]IUdR locoregionally administered to a human glioma in situ resembled those observed in a rat glioma model where administration of the radiopharmaceutical radiolabeled with the Auger electron emitter 125I was therapeutically effective.

Purification of recombinant human rhinovirus 14 3C protease expressed in Escherichia coli.

A gene encoding the human rhinovirus 14 (HRV14) sequence for expression of the viral polypeptide protein delta 3ABC was inserted into a plasmid driven by the heat-inducible bacteriophage lambda PL promoter. The coding sequence was also inserted into a pET vector for expression in the T7 system to produce 13C, 15N-labeled protein. The expressed HRV14 3C protease (3Cpro) autocatalytically cleaved itself from the polyprotein delta 3ABC, and the mature HRV14 3Cpro partitioned predominantly, in the case of the T7 system, in the insoluble fraction and exclusively, in the case of the PL system, in the insoluble fraction. The insoluble HRV14 3Cpro was solubilized in urea and purified using anion- and cation-exchange chromatography. The protease was refolded/activated and further purified using a size-exclusion column. HRV14 3Cpro was purified to > 90% homogeneity as shown by SDS-PAGE and to 95% by HPLC. A continuous fluorescence assay was developed which utilized an intramolecularly quenched 9-amino-acid substrate. The substrate anthranilic acid (Anc)-Thr-Leu-Phe-Gln-Gly-Pro-Val-(p-NO2)-Phe-Lys mimicked the natural 2C/3A cleavage site (Thr-Leu-Phe-Gln-Gly-Pro-Val-Tyr-Phe) using an N-terminal anthranilic acid donor group on one side of the scissile bond (Gln/Gly) and a p-NO2-Phe acceptor group at the P4 position. Measured by the fluorescence assay, HRV14 3Cpro had a Km of 300 microM for the substrate.

Transesophageal atrial pacing (TAP) for sinus bradycardia during coronary artery bypass grafting: comparison of TAP to intermittent bolus gallamine.

OBJECTIVE: To assess the relative efficacy of a pacing esophageal stethoscope and intermittent boluses (40 mg) of gallamine in correcting sinus bradycardia (SB) during coronary artery surgery. DESIGN: The study was prospective, randomized, and controlled. SETTING: A community hospital. PARTICIPANTS: Fifty patients scheduled for elective coronary artery surgery. INTERVENTIONS: The patients were randomly allocated to receive treatment for an SB (less than 60 BPM) with either transesophageal atrial pacing (TAP) or gallamine. MEASUREMENTS AND MAIN RESULTS: Heart rate, blood pressure, and systemic hemodynamics were measured. The electrocardiogram was monitored for rate, rhythm, and conduction abnormalities. Twenty-four of the 25 TAP patients could be paced at a rate of 70 BPM after SB. Cardiac index increased from 1.90 to 2.56 L/min/m2. In the gallamine group, heart rate was increased from 50 to 66 BPM, but cardiac index only increased to 2.2 L/min/m2, and 2 patients developed nodal rhythms. Eight of these patients had peak heart rates over 80 BPM, and two were over 90 BPM. CONCLUSIONS: The ability to reliably and precisely control heart rate was superior with TAP compared with intermittent bolus dosing with gallamine.

Thallium-201 technetium-99m HMPAO single-photon emission computed tomography (SPECT) imaging for guiding stereotactic craniotomies in heavily irradiated malignant glioma patients.

SPECT scanning with Tl-201 and Tc-99m offers a unique, inexpensive functional imaging modality to combine with CT stereotactic craniotomy for guiding resection of necrosis and/or tumour in patients treated with escalated doses of radiation (> 6000 cGy) by either brachytherapy or radiosurgery. Thirty-two cases were analyzed, with a detailed description of the imaging and operative techniques.

Detection of recurrent gliomas with quantitative thallium-201/technetium-99m HMPAO single-photon emission computerized tomography.

Deteriorating clinical status after high-dose radiation therapy for high-grade gliomas may be due to radiation changes or may signal recurrent or residual tumor mass. The two conditions cannot be distinguished reliably by computerized tomography (CT) or magnetic resonance (MR) imaging. The authors assessed the ability of sequential thallium-201 chloride (201Tl) and technetium-99m hexamethylpropylene amine oxime (99mTc HMPAO) single-photon emission CT (SPECT) to distinguish tumor recurrence from radiation changes after high-dose (greater than or equal to 600 cGy) radiation therapy for malignant gliomas. Preoperative tumor/nontumor uptake ratios were analyzed in 32 patients and correlated with the presence of gross tumor at the time of reoperation. In 12 of 13 patients with 201Tl tumor/scalp ratios of 3.5 or greater, recurrent tumor was present. The authors found 99mTc HMPAO SPECT to be useful for identifying the absence of solid tumor recurrence in patients with low to moderate 201Tl uptake (ratio 1.1 to 3.4) and low perfusion to that site. In 11 of 12 patients with 99mTc HMPAO tumor/cerebellum ratios of 0.50 or less, no recurrent tumor mass was present. Three of seven patients with 201Tl ratios of 3.4 or less and 99mTc HMPAO ratios of 0.51 or more had recurrent tumor found at surgery; thus the test was not predictive in this group. It is concluded that the use of sequential 201Tl and 99mTc HMPAO SPECT accurately identifies the presence of tumor recurrence versus radiation changes in most patients with high-grade astrocytomas who have undergone tumor resection and high-dose radiation therapy.

Computer-assisted superimposition of magnetic resonance and high-resolution technetium-99m-HMPAO and thallium-201 SPECT images of the brain.

A method for registering three-dimensional CT, MR, and PET data sets that require no special patient immobilization or other precise positioning measures was adapted to high-resolution SPECT and MRI and was applied in 14 subjects (five normal volunteers, four patients with dementia (Alzheimer's disease), two patients with recurrent glioblastoma, and three patients with focal lesions (stroke, arachnoid cyst and head trauma]. T2-weighted axial magnetic resonance images and transaxial 99mTc-HMPAO and 201Tl images acquired with an annular gamma camera were merged using an objective registration (translation, rotation and rescaling) program. In the normal subjects and patients with dementia and focal lesions, focal areas of high uptake corresponded to gray matter structures. Focal lesions observed on MRI corresponded to perfusion defects on SPECT. In the patients who had undergone surgical resection of glioblastoma followed by interstitial brachytherapy, increased 201Tl corresponding to recurrent tumor could be localized from the superimposed images. The method was evaluated by measuring the residuals in all subjects and translational errors due to superimposition of deep structures in the 12 subjects with normal thalamic anatomy and 99mTc-HMPAO uptake. This method for superimposing magnetic resonance and high-resolution SPECT images of the brain is a useful technique for correlating regional function with brain anatomy.

Metabolism of 99mTc-L,L-ethyl cysteinate dimer in healthy volunteers.

99mTc-L,L-Ethyl cysteinate dimer (ECD) is a brain-perfusion imaging agent, which exhibits selective retention in brain and rapid renal excretion. The pharmacokinetics and metabolism of ECD were studied in vivo in healthy humans and its metabolism in vitro was evaluated in tissue from human brain. In vitro studies showed 99mTc-L,L-ECD to be metabolized to a polar 99mTc-complex. It has been shown previously that most of the activity of 99mTc retained in the brain of the monkey in vivo is in the form of a polar 99mTc complex (Walovitch, Hill, Garrity, Cheesman, Burgess, O'Leary, Watson, Ganey, Morgan and Williams, 1989). Whole body images of the distribution of 99mTc-L,L-ECD (10 mCi i.v.) in four adult males showed good uptake in brain, with slow elimination (6.8 +/- 0.3% injected dose [mean +/- SE] at 5 min), with less than 25% decrease in activity during 4 hr of imaging. Background areas in the head and lungs washed out rapidly, providing ideal imaging conditions. Elimination of 99mTc from venous blood was biphasic, with a plateau of activity between 2-15 min (7-8% injected dose) before a terminal phase, with a t1/2 of a few hours. Organic extraction of whole venous blood showed greater than 50% of the 99mTc-L,L-ECD to be in the form of polar metabolite(s) at 5 min. They were identified in the urine as the 99mTc ethylenediylbis-L-cysteine, monoethyl ester complex (ECM) and the 99mTc-ethylenediylbis-L-cysteine complex (EC). These metabolites were excreted rapidly (75% injected dose in urine within 6 hr). The results of this study support the hypothesis that the selective retention in brain, rapid blood elimination and renal excretion of 99mTc-L,L-ECD is due to its metabolic transformation to polar end products.

Extracranial metastatic glioblastoma: appearance on thallium-201-chloride/technetium-99m-HMPAO SPECT images.

Sequential thallium-201-chloride and technetium-99m-hexamethylpropyleneamine oxime single-photon emission computed tomography (SPECT) images were obtained in a patient with extracranial metastatic glioblastoma multiforme. Thallium-201 uptake was high (three times the scalp background) in all pathologically confirmed extracranial metastases and moderate (1.6 times scalp background) intracranially, where most biopsy specimens showed gliosis with scattered atypical astrocytes. Technetium-99m-HMPAO uptake was decreased intracranially in the right frontal and parietal lobes which had been irradiated. It was also decreased in one well-encapsulated scalp lesion and high in another scalp mass with less defined borders. Possible mechanisms of tumor uptake of these agents are reviewed.

Brain perfusion SPECT using an annular single crystal camera: initial clinical experience.

The annular single-crystal brain camera (ASPECT) is a digital SPECT system with a single-crystal sodium iodide thallium Nal(Tl) ring detector and collimator system designed to view the patient's head from three angles simultaneously. The ring is rotated concentrically to the detector for three-dimensional reconstruction over a 21.4 cm (diameter) by 10.7 cm (length) field of view. We evaluated the system clinically by imaging a Hoffman brain phantom and seven subjects, of whom two were normal controls, three had previous cerebral infarction and two had dementia. The ASPECT system produced tomographic images of high spatial resolution. In normal subjects, the separation of striata from thalami by the posterior limbs of the internal capsules was much clearer on ASPECT images than on rotating gamma camera images. The high spatial resolution obtained with the ASPECT system translates into superior anatomical representation of the brain compared to the standard rotating gamma camera.

Myocardial clearance of Tc-99m hexakis-2-methoxy-2-methylpropyl isonitrile (MIBI) in patients with coronary artery disease.

Myocardial clearance of the new cationic, lypophilic myocardial perfusion agent, Tc-99m-hexakis-2-methoxy-2-methylpropyl isonitrile (MIBI) was studied in nine patients with coronary artery disease. Regional time-activity curves were determined from serial postexercise myocardial SPECT images after a single dose of Tc-99m MIBI. There were significant differences between the clearance rates from normal and ischemic myocardium. Tc-99m MIBI washout from normal myocardium was 27 +/- 8% by 6 hours after injection. Clearance from mild myocardial defects (initial activity greater than 60% of the activity in normal myocardium) was 16% by 6 hours in six patients. No washout was detected by 6 hours in the three patients with severe myocardial defects. The ratio between the activity in ischemic and normal myocardium increased from 0.70 +/- 0.08 to 0.80 +/- 0.13 and 0.84 +/- 0.13 at 4 and 6 hours after injection in the patients with mild defects. In the patients with large defects, the ratio increased from 0.42 +/- 0.09 to 0.54 +/- 0.07 at 6 hours. It is concluded that, while redistribution is substantially slower than with Tl-201, image interpretation and data evaluation should be approached cautiously when imaging is delayed 4 hours or more after injection of Tc-99m MIBI. Quantitative techniques aimed at evaluating the extent and intensity of myocardial ischemia will be particularly affected.

Development and validation of a Monte Carlo simulation of photon transport in an Anger camera.

The geometric component of the point spread function (PSF) of a gamma camera collimator can be determined analytically, and the penetration component can be calculated readily by numerical ray-tracing. A Monte Carlo simulation of photon transport which includes collimator scatter is developed. The simulation was implemented with an array processor which propagates up to 1024 photons in parallel, allowing accurate estimates of the total radial PSF in less than a day. The simulation was tested by imaging monoenergetic point sources of Tc-99m, Cr-51, and Sr-85 (140, 320, and 514 keV, respectively) on a General Electric Star Cam with low-energy, general-purpose, and medium-energy collimators. Comparisons of measured and simulated PSFs demonstrate the validity of the model and the significance of collimator scatter in the degradation of image quality.

Technetium-99m ECD: a new brain imaging agent: in vivo kinetics and biodistribution studies in normal human subjects.

Lipophilic neutral 99mTc complexes of diaminedithiol (DADT) ligands cross the brain-blood barrier. A new derivative of DADT family, 99mTc ethyl cysteinate dimer (ECD) showed high brain uptake in nonhuman primates. We report here the in vivo kinetics and biodistribution results in 16 normal human subjects. Dynamic images of brain obtained for 10 min following an i.v. administration of [99mTc]ECD showed that the maximum 99mTc brain activity reached within 1 min and remained near that level for the next 10 min. The blood clearance of the tracer was very rapid and the activity remaining in blood after 5 min was less than 10%. Within 2 hr 50% of 99mTc activity was excreted in urine. Anterior and posterior total-body images were obtained at 5, 30, 60 min, 2, 4, 24, and 48 hr using a moving table at 20 cm/min. Percent injected dose was calculated for different organs and tissues. The brain uptake was 6.5 +/- 1.9% at 5 min postinjection and remained relatively constant over several hours. Two-compartment analysis of brain time-activity curve showed that 40% of brain activity washed out faster (T 1/2 = 1.3 hr) while the remaining 60% had a slower clearance rate (T 1/2 = 42.3 hr). Some of the tracer was excreted through the hepatobiliary system. Lung uptake and retention of [99mTc]ECD was negligible. Radiation dosimetry is favorable for the administration of up to 20-40 mCi of [99mTc]ECD. These results show that [99mTc]ECD is rapidly extracted and retained by the brain providing favorable conditions for single photon emission computed tomography imaging.

Detection efficiency of a high-pressure gas scintillation proportional chamber.

The detection efficiency of a high-pressure, gas scintillation proportional chamber (GSPC), designed for medical imaging in the 30-150 keV energy range, has been investigated through measurement and Monte Carlo simulation. Measurements were conducted on a GSPC containing 4 atm of pure xenon separated from a hexagonal array of seven ultraviolet-sensitive photomultiplier tubes by 1.27-cm-thick fused-silica windows. Experimental measurements of the photopeak efficiency, fluorescence escape efficiency, and the energy collection efficiency were obtained. Results were also obtained for different photon energies and different values of temporal resolution. The measurements were compared with the results obtained from a Monte Carlo simulation designed specifically for investigating the imaging of low-energy photons (below 150 keV) with a gas-filled detector. The simulation was used to estimate photopeak efficiency, fluorescence escape efficiency, photopeak-to-fluorescence escape peak ratio, quantum interaction efficiency, energy collection efficiency, and local energy collection efficiency. The photopeak efficiency of the GSPC relative to that of a 3-in. (7.62-cm)-thick sodium iodide crystal was measured to be 0.284 +/- 0.001 at 60 keV and 0.057 +/- 0.001 at 140 keV. Of the 60-keV photons incident upon the detector, 70% +/- 4% interacted in the detector, with 28% +/- 1% being in the photopeak, as estimated both by experimentation and through the simulation. The maximum energy collection efficiency was found to be 65% at 60 keV, with 46% being deposited within 0.2 cm of the initial photon interaction. The information gained from this study is being used to design an optimized detector for use in specialized nuclear medicine studies.