Robert E. Zimmerman

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.

Technepine: A high-affinity 99mtechnetium probe to label the dopamine transporter in brain by SPECT imaging

Increasing evidence suggests that the dopamine transporter, localized on dopamine neurons, is a marker for a number of physiological and pathological states (KaufmanandMadras, 1991,1993; Madras et al., 1990a, Schoemaker et al., 1985; Singer et al., 1991). With the development of sensitive probes, brainimaging and mea- surement of the transporter have become feasible in re- cent years (Brownell et al., in press; Innis et al., 1991; Frost et al., 1993; Madras et al., 1991; Morns et al., sub- mitted; Seibyl et al., 1995; van Dyke et a1.,1995; Wonget al., 1993,1995). Drugs of many chemical classes, includ- ing cocaine, bind to the dopamine transporter (Seeman, 1993). Nevertheless, effective imaging agents have been developed almost exclusively from the phenyltropane analogue of cocaine WIN 35,428 or CFT, a potent dopa- mine transport inhibitor (Clarke et al., 1973; Heikkila et al., 1979). The impetus for developing [llC]WIN 35,428 as a PET ligand (Hantraye et al., 1992; Madras, 1994; Madras et al., 1991, 1994; Wong et al., 1993; Meltzer et al., 1993) and y-emitting analogues for SPECT imaging (e.g., RTI-55, the 4-iodophenyl analogue of WIN 35,428, Canfield et al., 1990; Boja et al., 1991; Innis et al., 1991) arose directly from our observations of the binding of WIN 35,428 to the dopamine transporter. Unlike previ- ous dopamine transport inhibitors (noncocaine conge- ners) proposed for brain imaging(Kuhar et a1.,1990), the radiolabeled form of WIN 35,428 binds to the dopamine transporter in brain striatum with very low levels of non- specific binding (Madras et al., 1989a,b) and distributes principally to dopamine-rich regions of brain, as we re- ported in 1989 (Canfield et al., 1989) and subsequently (Canfield et al., 1990; Kaufman et al., 1991; Kaufman and Madras, 1992). SPECT imaging techniques are more practical than PET for routine clinical studies because of the lesser

Characterization of human cells transformed by chemical and physical carcinogens in vitro

SummarySeveral different classes of chemical carcinogens induced the transformation of human fibroblasts grown in vitro. Characteristics of the events that occur from time of treatment through the expression of neoplastic transformation are presented. The S-phase appeared to be the portion of the cell cycle most vulnerable to insult. Staging of the cells by blocking them in G1 before releasing them to proceed through scheduled DNA synthesis (S) was required to induce reproducible transformation. Compounds such as insulin were added to the cells upon release from the block to sensitize the cells to the carcinogen that was added during S. Growth of the transformed cells as distinct from nontransformed cells was promoted by growth in medium supplemented with 8X nonessential amino acids. Carcinogen-treated cells in the early stage of transformation exhibited abnormal colony morphology and were able to grow at 41°C, in air atmosphere, and in medium supplemented with only 1% serum. In addition, the transformed cells were insensitive to KB cell lysate and exhibited density independent, as well as anchorage independent, growth (i.e., growth in 0.33% agar). Cells that grew in soft agar also produced undifferentiated mesenchymal tumors in preirradiated nude mice.

The use of photon absorptiometry in the diagnosis of renal osteodystrophy.

By using a 125I collimated point source to measure bone mineral, 700 measurements were obtained from the cortical bone of the lower arm in 303 patients with renal failure representing every stage of the disease. Of these patients, 123 had received transplants. The following conclusions can be drawn: (a) Prolonged azotemia leads to severe loss of bone mineral, which, in early stages, is only detectable using photon absorptiometry. (b) Gradual loss of bone mineral occurs during dialysis, (c) Parathyroidectomy slows this loss but fails to reverse it. (d) After transplantation, the rate of bone loss will either decrease or cease, but few patients show any increase in bone mineral. (e) Preliminary biochemical data on these patients show a relationship between bone mineral and creatinine, serum phosphate and serum calcium values.

Utilization of parasternal lymphoscintigraphy in radiation therapy of breast carcinoma.

In radiation therapy of patients with breast carcinoma, the ipsilateral internal mammary lymph nodes are either irradiated by a separate anterior field or included by isocentric opposing tangential fields, which also treat the breast and chest wall. To determine the acceptability of a particular treatment setup, the positions of the nodes must be determined with respect to the treatment fields. For the anterior field technique the problem is two-dimensional and is solved by simply superimposing the treatment field onto an anterior lymphoscintigram. For treatment by opposing tangential fields the problem is three-dimensional and more complex. The solution described in this note is to project the three-dimensional lymph node positions, obtained by a stereo-lymphoscintigraphic procedure, onto the tangential field radiographs. A mathematical expression is given to perform the required projection of the node positions onto the radiographs.

Count-rate dependent event mispositioning and NEC in PET

Most current PET detector designs suffer from event mispositioning at high count rates, as scintillation light from nearby and nearly simultaneous gamma ray conversions becomes mixed. We have used the NEMA NU 2-2001 70 cm test phantom and a Na-22 point source to quantify this effect as a function of activity on two block-detector tomographs (the Siemens/CTI HR+ and the General Electric Discovery LS), and two Anger-type PET tomographs (the Siemens ECAM DUET and the Philips CPET+). After accounting for event losses due to dead time, we find that the number of counts on LORs passing through a cylinder of diameter and height equal to the point-source full width at tenth-maximum measured at low rate surrounding the point source decreases by between 9% (HR+) and 35% (CPET+) at the activity giving rise to peak noise equivalent count (NEC) rate. Mispositioned events act to reduce signal-to-noise ratio, both by reducing apparent activity at the originating location and by increasing the signal background. We have reformulated the conventional expression for NEC rate to account for this phenomenon. The new formulation of NEC, which we call NEC/sup */, results in a lower peak value which in turn occurs at a lower activity concentration than for the conventional formulation.

A simulation-based assessment of the revised NEMA NU-2 70 cm long test phantom for PET

A 70 cm long polyethylene cylinder of radius 10 cm containing an off-center line source has been suggested for the characterization of PET tomograph whole-body performance in terms of scatter fraction, sensitivity to randoms and count-rate capability. In this work we perform a series of Monte Carlo simulations of a full-ring BGO system operating in 3D mode and a full-ring sodium iodide system operating in 3D mode to determine how closely scatter fraction and NEC results from the 70 cm cylinder follow those found in anthropomorphic activity and attenuation distributions. We find that the 70 cm cylinder measurements correctly rank-order the tomographs in terms of scatter fraction and NEC performance, but do not always accurately predict the actual scatter fractions or the peak NEC values encountered in the anthropomorphic models. Peak NEC for the phantom occurs at around double the activity concentrations which give rise to peak NEC in the anthropomorphic objects.

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

SummarySPECT scanning with TI-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.

The role of calcium and fluoride in osteoporosis in rhesus monkeys.

Twenty-two female Rhesus monkeys were fed purified diets varying in calcium and fluoride content for five years and studied, using radiographic, photon absorptiometric and histologic techniques. The results suggested that: 1) the addition of fluoride (50 ppm) to a diet containing 1 per cent calcium resulted in a reduction in bone growth rate and resorption, without affecting bone size or density nor resulting in fluorosis; 2) a diet containing 0.15 per cent calcium resulted in osteoporosis due to an increase in bone resorption; and 3) fluoride added to a similar low calcium diet prevented osteroporosis by reducing bone growth rate and resorption resulting in bones with normal density, but at the same time fluoride interfered with mineralization of osteoid leading to osteomalacia.

THE USE OF PHOTON DENSITOMETRY TO EVALUATE BONE MINERAL IN A GROUP OF PATIENTS WITH SPINAL CORD INJURY

Using two systems which depend on photon absorption techniques for measuring bone mineral, it has been demonstrated that in a group of patients with spinal cord injury there is loss of trabecular bone with preservation of cortical bone. The reason for this is as yet unexplained but may in part be related to the primary injury being that of the central nervous system.