Imaging techniques for the radioimmunodetection of cancer.

Problems in the radioimmunodetection of cancer typically involve small lesions having low object contrast. As such, the imaging device utilized must have a high spatial resolution as well as high detection efficiency. In addition, the imaging device must be interfaced to a computer system to allow data manipulation to include background substraction, contrast enhancement, and organ subtraction techniques to be used. While the conventional scintillation camera is the most widely used imaging device in conventional nuclear medicine imaging procedures, this system does not provide adequate imaging performance for radioimmunodetection of cancer. This is true since these devices typically do not provide adequate object contrast when detecting small lesions in the presence of moderately high background activity. The Pho/Con (Searle Radiographics) is a tomographic imaging device which, when interfaced to a computer system, is capable of providing adequate lesion detection for this specialized procedure. The newest version of this tomographic imaging system has a spatial resolution and a detector efficiency which are comparable to those of the conventional scintillation camera. The system has the added advantage of relatively constant high-spatial-resolution performance as well as high sensitivity over a wide range of depths. In addition, the imaging process involves a rectilinear scanning motion which results in inherently uniform response in each plane of interest. These combined properties result in high detection of small lesions in cases where the object contrast is extremely low. These inherent imaging properties when combined with the improved contrast provided with computer manipulation of data make this system ideal for radioimmunodetection problems. In this paper, the importance of spatial resolution, count density, lesion size, and object contrast are discussed in relation to the detectability of lesions in radioimmunodetection of cancer. In addition, the characteristics of the Pho/Con and its advantages in lesion detection are described.

Evaluation of myocardial ischemia using a rest metabolism/stress perfusion protocol with fluorine-18 deoxyglucose/technetium-99m MIBI and dual-isotope simultaneous-acquisition single-photon emission computed tomography.

OBJECTIVES: This study sought to develop a dual-isotope single-acquisition single-photon emission computed tomographic (SPECT) protocol using a multihead SPECT camera equipped with an ultra-high energy collimator to evaluate rest metabolism/stress perfusion simultaneously with fluorine-18 (F-18) deoxyglucose/technetium-99m (Tc-99m) 2-hexakis-2-methoxy-2-methylpropyl isonitrile (MIBI). BACKGROUND: The most accurate and logistic method of identifying injured but viable myocardium remains a diagnostic challenge. METHODS: Sixty-five patients were given 25 to 50 g of glucose and, after approximately 60 min, an injection of 370 MBq (10 mCi) of F-18 fluorodeoxyglucose. After a 35-min distribution phase, patients underwent exercise or pharmacologic stress followed by administration of 925 MBq (25 mCi) of Tc-99m MIBI. Five patients underwent F-18 fluorodeoxyglucose position emission tomography before dual-isotope SPECT: RESULTS: With a window of 20% for both photopeaks and a technetium-99m/fluorine-18 concentration of 3.2:1, the "spillover" from fluorine-18 into the technetium-99m window is < 6% of the total counts in the window in patients with a normal distribution of both radiopharmaceuticals. Phantom images clearly demonstrated cardiac defects measuring 2 x 1 and 2 x 0.5 cm. There was no significant difference in the images of the five patients who underwent both positron emission tomography and SPECT: Fifty-seven patients (mean [+/- SD] age 55 +/- 15 years, range 25 to 83; 38 men, 19 women) had satisfactory images and were included in the study. Twenty-one patients had normal study results; 15 had mismatched defects; 14 had matched defects; and 7 had both matched and mismatched defects. Twenty-three patients (mean age 54 +/- 6 years, range 30 to 83; 14 men, 9 women) underwent coronary angiography within 3 months of dual-isotope SPECT: There were seven normal studies, eight with mismatched defects, one with a matched defect and seven with matched and mismatched defects. When stenosis > 70% was used as the criterion for a diagnosis of coronary artery disease, dual-isotope SPECT had a sensitivity of 100%, specificity of 88%, positive predictive value of 93%, negative predictive value of 100% and an accuracy of 96%. CONCLUSIONS: Dual-isotope SPECT may provide an alternative, accurate, cost-effective method to nitrogen-13 ammonia/F-18 fluorodeoxyglucose positron emission tomography or thallium-201 reinjection for identifying injured or dysfunctional but viable myocardium.

Multimodality imaging of the thyroid and parathyroid glands.

Nuclear imaging of the thyroid and parathyroid glands has evolved from early radionuclide rectilinear thyroid scanning to the recently developed dual isotope subtraction technique for detecting parathyroid lesions. At the same time, x-ray fluorescent scanning, ultrasound, x-ray computed tomography, and magnetic resonance imaging have improved identification of these endocrine organs. The appropriate use and relative role of these imaging modalities in the investigation of patients with thyroid and parathyroid diseases is discussed.

Simultaneous emission and fluorescent scanning of the thyroid.

A comparison study of lithium-drifted silicon [Si(Li)] and high purity germanium (HpGe) was performed to explore the feasibility of replacing the current Si(Li) detector with the higher-efficiency HpGe detector. The improved efficiency of HpGe permits the use of collimators with higher resolution, which results in improved image quality over that achieved by the current Si(Li) system in use at Vanderbilt with an overall reduction in sensitivity of 29%. Since a 10 mm thick HpGe detector is about 75% efficient at 140 keV, the added advantage exists of simultaneously (a) imaging the stable-iodine distribution within the thyroid by x-ray fluorescence, and (b) the distribution of administered radiotracers such as [99mTc] pertechnetate. This comparison study shows that HpGe can compete with Si(Li) in overall detector efficiency, with the added benefits of better collimation to improve spatial resolution plus the simultaneous imaging of Tc-99m, all at the same equipment cost.

Image fusion using an integrated, dual-head coincidence camera with X-ray tube-based attenuation maps.

UNLABELLED: The purpose of this study was to characterize a dual-head gamma camera capable of FDG imaging using coincidence detection and equipped with an integrated x-ray transmission system for attenuation correction, anatomic mapping, and image fusion. METHODS: Radiation dose (425 mrads skin dose) and tissue contrast (0.7% deviation from expected values) were assessed for the x-ray system. Registration of transmission and emission scans was validated using a hot sphere phantom and was verified in selected patient studies. RESULTS: Fusion of anatomic maps and FDG images allowed precise anatomic localization of lesions identified using dual-head coincidence imaging. CONCLUSION: The combined approach of x-ray attenuation, anatomic mapping, and image fusion with scintigraphic studies provides a new diagnostic tool for nuclear medicine and fertile ground for future research.

Prediction of benignancy of the solitary "cold" thyroid nodule by fluorescent scanning.

A quantitative x-ray fluorescent scanning technique has been used routinely to determine iodine content ratios (ICR) of nodule to normal thyroid tissue in patients with solitary "cold" thyroid nodules. A study of 150 patients with histological diagnoses has shown that an ICR above 0.60 is an excellent indicator of benignancy with a sensitivity of 63% and a specificity of 99%. This technique, in conjunction with careful clinical judgment, can be used to identify those patients that are at low risk for malignancy and can probably undergo conservative clinical management.

FDG PET and dual-head gamma camera positron coincidence detection imaging of suspected malignancies and brain disorders.

UNLABELLED: The purpose of the study was to compare the diagnostic accuracy of fluorodeoxyglucose (FDG) images obtained with a dual-head coincidence gamma camera (DHC) with those obtained with a dedicated PET in a series of 26 patients. METHODS: Nineteen patients with known or suspected malignancies and 7 patients with neurological disorders underwent PET imaging after injection of approximately 10 mCi of FDG. Whole-body imaging was performed on 19 patients and brain imaging on 7 patients. DHC images were then acquired for 30 min over the region of interest using a dual-head gamma camera equipped with 3/8-in.-thick NaI(TI) crystals and parallel slit-hole collimators. The images were reconstructed in the normal mode, using photopeak/photopeak, photopeak/Compton and Compton/photopeak coincidence events. RESULTS: Although the spatial resolutions of PET with a dedicated PET scanner and of DHC are in the same range, the lesion detectability remains superior with PET (4 mm for PET versus 13.5 mm for DHC in phantom experiments) with a contrast ratio of 5:1. This is most probably attributable to the higher sensitivity of PET (2238 coincidences/min/microCi for PET versus 89 coincidences/min/microCi for DHC). The pattern of uptake and interpretation for brain imaging was similar on both PET and DHC images in all patients. In the 19 oncology patients, 38 lesions ranging from 0.7 to 5 cm were detected by PET. DHC imaging detected 28 (73%) of these lesions. Among the 10 lesions not seen with DHC, 5 were less than 1.2 cm, 2 were located centrally within the liver and suffered from marked attenuation effects and 3 were adjacent to regions with high physiological activity. The nondetectability of some lesions with DHC compared with PET can be explained by several factors: (a) start of imaging time (mean+/-SD: 73+/-16 min for PET versus 115+/-68 min for DHC, leading to FDG decay to 6.75 mCi for PET and 5.2 mCi for DHC); (b) limited efficiency of a 3/8-inch-thick Nal(TI) crystal to detect 18F photons; (c) suboptimal two-dimensional reconstruction algorithm; and (d) absence of soft-tissue attenuation correction for centrally located lesions. CONCLUSION: FDG DHC imaging is a promising technique for oncological and brain imaging.

Differentiation between malignant and benign solitary thyroid nodules by fluorescent scanning.

A quantitative fluorescent technique has been developed for making in vivo iodine content determinations of the total thyroid gland or of selected parts. In solitary thyroid nodules "cold" to radionuclide studies, the ratio of iodine content in the nodule to that in a corresponding area of the contralateral lobe has proven to be a good indicator of malignancy. In a preliminary study of 42 surgical patients, an iodine content ratio (ICR) below 0.60 (chosen a posteriori) proved to be an excellent indication of malignancy with a sensitivity of 100%, a specificity (predictive value) of 79%, and an overall accuracy of 90%. Further definitive studies are needed to verify these preliminary observations.

The effects of gating delays on ejection estimates: concise communication.

We have examined the effects of gating delays on the left-ventricular ejection fraction as measured by gated blood-pool studies. Patients with normal ventricular function were shown to have greater errors introduced by gate delays than those with poor function. The magnitude of the error depends on the shape of the ventricular time-activity curve. Actual delay measurements were performed on several commercial gates.

Clinical magnetic resonance imaging with nuclear medicine correlation.

The current role of magnetic resonance imaging (MRI) in different organ systems is discussed and compared to nuclear medicine and to other available clinical diagnostic modalities. The value of optimizing radiofrequency pulse sequence selection to provide additional tissue characterization is also described. The results of nuclear medicine and MRI studies in 56 patients are compared to evaluate the clinical diagnostic contribution of each imaging modality for various pathological processes. In addition, the state-of-the-art MRI systems and future development in MRI technology with its potential contribution is defined.

Rest myocardial perfusion/metabolism imaging using simultaneous dual-isotope acquisition SPECT with technetium-99m-MIBI/fluorine-18-FDG.

UNLABELLED: The purpose of this study was to develop a dual-isotope simultaneous acquisition (DISA) protocol using a multihead SPECT camera equipped with an ultrahigh-energy (UHE) collimator to evaluate simultaneously rest cardiac perfusion and metabolism with 99mTc-MIBI/18FDG. METHODS: Physical measurements were first performed with phantoms to develop the acquisition protocol. Fifteen patients underwent DISA-SPECT with 99mTc-MIBI/18FDG to validate the protocol. To evaluate the quality of the 99mTc-MIBI images acquired with the UHE collimator, four patients underwent a resting 99mTc-MIBI scan acquired with a high-resolution, low-energy collimator prior to DISA-SPECT. RESULTS: With a window of 20% for both photopeaks and a 99mTc/18F concentration ratio of 3.2:1, the spillover from 18F into the 99mTc window is 6% of the counts in the window for normal subjects. Phantom images clearly demonstrated defects measuring 2 x 1 and 2 x 0.5 cm. Technetium-99m-MIBI images obtained with the UHE and high-resolution collimators provided similar diagnostic information. Using a stenosis of > 70% as criteria to diagnose coronary artery disease, DISA-SPECT had a sensitivity of 100% and a positive predictive value of 93%. CONCLUSION: Simultaneous evaluation of rest myocardial perfusion/metabolism with a multihead SPECT camera equipped with an UHE collimator is possible using 99mTc-MIBI/18FDG with a dual-isotope simultaneous acquisition protocol.

FDG-SPECT: correlation with FDG-PET.

UNLABELLED: The clinical utility of FDG-PET imaging in the evaluation of patients with cardiac, oncologic and neurologic diseases is well documented. The major disadvantages of PET continue to be its high cost and limited availability. METHODS: With the goal of providing equivalent diagnostic information using a widely available, less expensive modality, we evaluated the clinical utility of FDG-SPECT imaging with a conventional dual-headed camera as compared to PET in 21 patients. RESULTS: To compare the image quality of the two modalities, major physical parameters and phantom determinations were obtained. By using the 511-keV collimators, we achieved resolution and system volume sensitivity that were less than those for PET by factors of 2.6 and 8, respectively. The SPECT system, on the other hand, could easily resolve 2 x 0.5-cm cold defects in the heart phantom and 2-cm hot lesions in a 22-cm cylindrical phantom with a target-to-background ratio of 5:1. FDG-SPECT imaging of nine patients with heart disease yielded similar diagnostic information of the amount of viable myocardium present when compared to PET. In seven of eight patients, malignant tissue visualized with FDG-PET was seen equally well with SPECT. The lesions not visualized with FDG-SPECT were either small (< or = 1.5 cm) or benign. SPECT imaging of four patients with cerebral lesions was inconclusive due to the small sample size but seemed promising. CONCLUSION: FDG-SPECT with 511-keV collimation is less expensive, more available and technically simpler than PET. We believe that FDG-SPECT has achieved sufficient sensitivity and resolution to detect myocardial viability and diagnose malignant tumors > or = 2 cm in diameter.

Evaluation of intrathoracic goiter with I-123 scintigraphy and nuclear magnetic resonance imaging.

Iodine-123 thyroid scintigraphy allows the diagnosis of a functioning retrosternal goiter in a patient with a mediastinal mass. The case report of a 60-yr-old lady demonstrates this. The correlative values of nuclear magnetic resonance imaging and thyroid scintigraphy in the initial evaluation and continued management of patients with thyroid mediastinal mass are presented. In addition, this observation demonstrates the ability of nuclear magnetic resonance to identify retrosternal thyroid tissue. This may obviate the need for TCT evaluation, which involves both ionizing radiation and iodinated contrast enhancement.

Fluorine-18-fluorodeoxyglucose cardiac imaging using a modified scintillation camera.

Conventional 201TI and hexakis 2-methoxy-2-isobutyl isonitrile studies are less accurate as compared to FDG PET in the prediction of functional recovery after revascularization in patients with injured but viable myocardium. The introduction of a dual-head variable-angle-geometry scintillation camera equipped with thicker crystals (5/8 in.) and high-resolution, ultrahigh-energy collimators capable of 511 keV imaging has permitted FDG SPECT to provide information equivalent to that of PET for the detection of injured but viable myocardium in patients with chronic ischemic heart disease. The development of standardized glucose-loading protocols, including glucose-insulin-potassium infusion and the potential use of nicotinic acid derivatives, has simplified the method of obtaining consistently good-to-excellent quality FDG SPECT cardiac studies. FDG SPECT may become the modality of choice for evaluating injured but viable myocardium because of enhanced availability of FDG, logistics, patient convenience, accuracy and cost-effectiveness compared to PET.

Instrumentation for coincidence imaging with multihead scintillation cameras.

Positron emission tomography (PET) has been used as a tool by investigators for many years to study metabolic processes in the body primarily with the radiopharmaceutical 18-fluordeoxyglucose. However, use of this technology has not been widespread because of the high expense of the equipment and its limitation to the imaging of positron emitters only. Recent improvements in scintillation camera technology have now made it possible to produce hybrid multihead cameras that can function in a coincidence mode for the detection of the annihilation radiation from positron emitters and in the normal mode for routine single-photon imaging. Although still limited in sensitivity, these camera systems continue to be improved and the recent addition of iterative reconstruction algorithms and attenuation correction capability have resulted in significant improvements in image quality. The integration of a low resolution computed tomography (CT) scanner with a dualhead camera by 1 manufacturer now makes it possible to perform attenuation correction and image fusion of anatomy and function into 1 image to improve the anatomic localization of abnormalities detected with coincidence imaging. Investigators continue to work on improved electronics and new types of detectors to further improve the sensitivity of these systems. These developments coupled with continued improvements in PET technology have resulted in the availability of a broad spectrum of systems for the investigator to consider when purchasing a system with positron imaging capability.

18-Fluorodeoxyglucose imaging with positron emission tomography and single photon emission computed tomography: cardiac applications.

The assessment of myocardial viability has become an important aspect of the diagnostic and prognostic work-up of patients with ischemic cardiomyopathy. Although revascularization may be considered in patients with extensive viable myocardium, patients with predominantly scar tissue should be treated medically or evaluated for heart transplantation. Among the many viability tests, noninvasive assessment of cardiac glucose use (as a marker of viable tissue) with F18-fluorodeoxyglucose (FDG) is considered the most accurate technique to detect viable myocardium. Cardiac FDG uptake has traditionally been imaged with positron emission tomography (PET). Clinical studies have shown that FDG-PET can accurately identify patients with viable myocardium that are likely to benefit from revascularization procedures, in terms of improvement of left ventricular (LV) function, alleviation of heart failure symptoms, and improvement of long-term prognosis. However, the restricted availability of PET equipment cannot meet the increasing demand for viability studies. As a consequence, much effort has been invested over the past years in the development of 511-keV collimators, enabling FDG imaging with single-photon emission computed tomography (SPECT). Because SPECT cameras are widely available, this approach may allow a more widespread use of FDG for the assessment of myocardial viability. Initial studies have directly compared FDG-SPECT with FDG-PET and consistently reported a good agreement for the assessment of myocardial viability between these 2 techniques. Additional studies have shown that FDG-SPECT can also predict improvement of LV function and heart failure symptoms after revascularization. Finally, recent developments, including coincidence imaging and attenuation correction, may further optimize cardiac FDG imaging (for the assessment of viability) without PET systems.

Radionuclide measurement of differential glomerular filtration rate in urinary tract obstruction.

In a previous study using dogs whose renal function was rendered asymmetric by unilateral infarction, the efficacy of technetium-99m (99mTc) DTPA and DMSA in measuring differential glomerular filtration rate (GFR) was demonstrated. The present study was undertaken to determine whether the same techniques were applicable to unilateral ureteral obstruction. Five normal dogs and nine dogs with partial unilateral ureteral obstruction had determination of glomerular filtration rate by standard techniques using constant infusions of iothalamate and creatinine after ureteral catheterization. These results were compared with total GFR as measured by single injection of 99mTc DTPA and analysis of the plasma disappearance curve. Calculated differential GFR was obtained by multiplying total GFR from double exponential analysis of this curve (DTPA2) by each of three measures of differential function. These included the percent differential uptake of 99mTc DTPA and 99mTC DMSA in the posterior projection as well as the geometric mean of 99mTc DMSA uptake. There were good correlations between differential GFR determined by iothalamate clearances at ureteral catheterization and all noninvasive methods involving radionuclides and DTPA2 ( r = 0.93-0.99). Single exponential analysis of the 99mTc DTPA plasma disappearance curve was less satisfactory than double exponential analysis. These results and those reported previously support the use of radionuclides in the determination of differential GFR in a variety of clinical situations.

Radionuclide measurement of differential glomerular filtration rate.

The authors sought to determine whether radionuclides could provide a reasonable estimate of differential renal function in five normal dogs and six dogs with unilateral segmental renal infarction. Glomerular filtration rate (GFR) of each kidney was measured by the standard technique using constant infusions of 99mTc-DTPA, iothalamate, and creatinine following ureteral catheterization. These results were correlated with total GFR estimated by bolus injection of 99mTc-DTPA and analysis of the plasma 99mTc-DTPA disappearance curve obtained by blood sampling. Differential GFR was then calculated by multiplying the total GFR from double exponential analysis of this curve (DTPA2) by each of three measures of differential function. These include the percent differential uptake of 99mTc-DTPA and 99mTc-DMSA in the posterior projection as well as the geometric mean of 99mTc-DMSA uptake. There were good correlations between differential GFR calculated from iothalamate clearances obtained at ureteral catheterization and all noninvasive methods involving radionuclides and DTPA2 (r = 0.85 - 0.99). Single exponential analysis of the 99mTc-DTPA plasma disappearance curve was less satisfactory. The authors suggest that measurement of total and differential GFR calculated from plasma clearance of 99mTc-DTPA and external counting may be a useful method with potential clinical applications.

Craniotomy flap osteomyelitis: a diagnostic approach.

Nine cases of suspected craniotomy flap osteomyelitis evaluated by combined bone and gallium scanning are presented. In six cases, the clinical data were inconclusive and evaluation by radionuclide imaging provided an accurate negative diagnosis. The other three cases considered positive by this technique were proven infected at subsequent exploration and flap removal. The use of radionuclide bone and gallium imaging should be considered in cases of possible craniotomy flap osteomyelitis.

Carcinoma of the thyroid with description of a new scanning technic.

A statistical analysis of 193 patients with thyroid carcinoma encountered at Vanderbilt University Hospital from 1925 to 1974 is reported, from which the following conclusions are drawn: (1) Papillary thyroid carcinoma is an extremely favorable lesion that when grossly limited to one thyroid lobe can usually be managed successfully by ipsolateral total lobectomy. (2) Cervical lymph node enlargement in patients with papillary carcinoma requires lymph node dissection. When feasible, the spinal accessory nerve should be preserved. (3) Failure to cure papillary and follicular thyroid carcinoma is influenced by advanced age, inadequate local extirpation, and unresectability of the carcinoma. (4) Prophylactic lymph node dissection is rarely indicated in the treatment of follicular carcinoma. A new isotope scanning procedure, developed at Vanderbilt University Hospital, promises to be helpful in preoperatively differentiating benign from malignant solitary thyroid nodules.