A pragmatic protocol for I-131 rhTSH-stimulated ablation therapy in patients with renal failure.

PURPOSE: Ablation of thyroid remnants in patients with differentiated thyroid carcinoma and renal failure can be challenging because of the altered and variable clearance rates of iodine from the blood secondary to variations in dialysis protocols, which complicate the selection of the appropriate I-131 dose. The advent of recombinant human TSH allows a simpler approach to dosimetry and ablation without rendering the patient hypothyroid. Avoidance of hypothyroidism may be an important consideration for patients who are experiencing various morbidities from conditions associated with renal failure. METHOD: Three patients on dialysis, who had undergone total thyroidectomy and were euthyroid on L-thyroxine replacement, were given diagnostic doses of I-131 followed by blood and whole-body retention measurements through serial dialyses to determine individual blood clearance rates. After administration of rhTSH, each patient received an ablative dose of I-131 calculated to keep total body dose below 1 Gy. RESULTS: The treatments were administered without complications, and in follow-up imaging of 2 available patients, the ablations were demonstrated to be complete. CONCLUSION: Dosimetry performed on euthyroid dialysis patients permits I-131 dose selection and avoids the additional morbidity of hypothyroidism.

A case of bronchopulmonary carcinoid tumor: the role of octreotide scanning in localization of an ectopic source of ACTH.

BACKGROUND: Bronchopulmonary carcinoids are neuroendocrine tumors. They can present with Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) secretion. Curative resection is possible only after adequate localization of the ectopic source. OBJECTIVE: To describe a case that illustrates the role of octreotide scanning in the management of a bronchopulmonary carcinoid. RESULTS: The use of preoperative and postoperative octreotide scanning aided in performing a limited resection, thereby preserving the lung parenchyma. CONCLUSIONS: We propose that octreotide scanning can be a very important and informative test in the management of carcinoid tumors. In situations when conventional imaging is not conclusive, octreotide scanning may be of help in determining the source of ectopic ACTH syndrome.

Two cases of thyroid carcinoma that were not stimulated by recombinant human thyrotropin.

Recombinant human TSH (rhTSH) is being widely used to monitor patients who were previously treated for differentiated thyroid cancers for evidence of recurrence. Its value lies in the avoidance of recurrent episodes of hypothyroidism in the follow-up protocols. rhTSH is also being evaluated as a potential therapeutic adjunct that would spare patients the experience of becoming hypothyroid when undergoing thyroid remnant ablation or treatment for metastases. In some centers, rhTSH is also used to support compassionate care of patients with advanced disease who cannot safely become hypothyroid. The (131)I uptake response to rhTSH, presently an off-label application, is expected to be similar to that of endogenously raised TSH levels. The two cases presented here are cautionary tales in which (131)I uptake by metastases was present under hypothyroid conditions, but absent in one patient and present in only a portion of the lesions in the other, with rhTSH stimulation.

FDG PET of recurrent or metastatic 131I-negative papillary thyroid carcinoma.

UNLABELLED: This study reports on the use of FDG PET in the follow-up of papillary thyroid cancer patients with negative findings on 131I total body scans and elevated levels of thyroglobulin after total thyroidectomy. METHODS: Eleven asymptomatic patients with previous papillary thyroid cancer, total thyroidectomy, 131I ablation, and treatment of all known metastases had negative findings on 131I total body scans after therapy but persisting elevations of thyroglobulin when not receiving thyroid hormone. All imaging before PET failed to show persisting tumor. FDG PET was performed on all patients while receiving full thyroid hormone replacement, except for the repeated scan of 1 patient (patient 6). After the PET scan, all patients were referred for supplementary CT, sonography, or biopsy of lesions in the neck. RESULTS: All 11 patients showed FDG uptake in the neck or upper mediastinum-in the initial scan in 10 and in a repeated scan in 1. Sonographically guided biopsy confirmed malignancy in 6, was nondiagnostic in 2, and showed normal findings in 1. In 2 patients, the sonographic results were normal and no biopsy was attempted. FDG imaging redirected the treatment of 7 patients, resulting in surgery and external beam radiotherapy in 3, surgery in 1, and external beam radiotherapy in 2. One patient declined further recommended surgery. The other 4 patients remain under observation. Surgical histopathology confirmed thyroid tumor in all 4 surgically treated patients. Retrospective review of the original histopathology slides showed no preponderance of aggressive histology. CONCLUSION: FDG PET is able to guide further evaluation of thyroid cancer patients who have elevated thyroglobulin levels and normal findings on 131I whole-body scanning.

Java-based remote viewing and processing of nuclear medicine images: toward "the imaging department without walls".

UNLABELLED: In nuclear medicine practice, images often need to be reviewed and reports prepared from locations outside the department, usually in the form of hard copy. Although hard-copy images are simple and portable, they do not offer electronic data search and image manipulation capabilities. On the other hand, picture archiving and communication systems or dedicated workstations cannot be easily deployed at numerous locations. To solve this problem, we propose a Java-based remote viewing station (JaRViS) for the reading and reporting of nuclear medicine images using Internet browser technology. METHODS: JaRViS interfaces to the clinical patient database of a nuclear medicine workstation. All JaRViS software resides on a nuclear medicine department server. The contents of the clinical database can be searched by a browser interface after providing a password. Compressed images with the Java applet and color lookup tables are downloaded on the client side. This paradigm does not require nuclear medicine software to reside on remote computers, which simplifies support and deployment of such a system. To enable versatile reporting of the images, color tables and thresholds can be interactively manipulated and images can be displayed in a variety of layouts. Image filtering, frame grouping (adding frames), and movie display are available. Tomographic mode displays are supported, including gated SPECT. RESULTS: The time to display 14 lung perfusion images in 128 x 128 matrix together with the Java applet and color lookup tables over a V.90 modem is <1 min. SPECT and PET slice reorientation is interactive (<1 s). JaRViS could run on a Windows 95/98/NT or a Macintosh platform with Netscape Communicator or Microsoft Intemet Explorer. The performance of Java code for bilinear interpolation, cine display, and filtering approaches that of a standard imaging workstation. CONCLUSION: It is feasible to set up a remote nuclear medicine viewing station using Java and an Internet or intranet browser. Images can be made easily and cost-effectively available to referring physicians and ambulatory clinics within and outside of the hospital, providing a convenient alternative to film media. We also find this system useful in home reporting of emergency procedures such as lung ventilation-perfusion scans or dynamic studies.

Radiation safety when a patient dies after therapy.

OBJECTIVE: When a patient dies a short time after radionuclide therapy, several issues arise due to the shifting of responsibility from patient care to protection of the public, while respecting societal values and rites. Such a situation occurred in our institution after administering a large therapeutic dose of 131I for metastatic thyroid cancer. The requirements of safe practice, the shift accountability, the ethical aspects and forthcoming changes in the regulatory constraints are discussed.

Early detection of cancer cachexia in the rat using 31P magnetic resonance spectroscopy of the liver and a fructose stress test.

The dynamic metabolic effects of a fructose infusion challenge on hepatic intracellular levels of adenosine 5'-triphosphate (ATP), inorganic phosphate (Pi) and phosphomonoesters (PME) were monitored noninvasively by 31P MRS in a remote tumour-bearing rat model. Fisher male rats were inoculated with a methylcholanthrene-induced sarcoma. Seventeen rats were randomized into three groups: control (n = 6), low tumour burden (LTB, n = 6), or moderate tumour burden (MTB, n = 5). The LTB group had tumour burdens of 0.2-2.0% while the MTB group had tumour burdens of 2.6-5.7%. All rats were in the pre-clinical phase of cancer cachexia as determined by food intake and body weight. Rats were infused with 1.2 g/kg of fructose i.v. and the metabolic response of the liver was monitored with time over 1 h via 31P MRS. In all groups an immediate increase in hepatic levels of PME was noted, which returned to baseline values over the course of the experiment, reflecting the phosphorylation of fructose to fructose 1-phosphate. For the MTB rats, the return to baseline levels was more rapid than in the control or LTB group. All groups experienced a 20% decrease in hepatic ATP levels which did not return to baseline over the 1 h observation period. As well, all groups experienced an initial fall in Pi, which recovered to prefructose levels or greater. MTB rats demonstrated a 30-40% increase in Pi concentration and a 60-70% increase in Pi/ATP ratio after infusion with fructose as compared to LTB and control rats (ANOVA;p<0.05). This is consistent with cachexia-induced enhancement of hepatic gluconeogenic activity, and hence more rapid release of Pi from the phosphorylated metabolites in the MTB rats. Thus fructose infusion and hepatic 31P MRS permit pre-clinical detection of cancer cachexia as reflected by increased Pi generation and more rapid removal of PME.

Effect of anaemia correction on skeletal muscle metabolism in patients with end-stage renal disease: 31P magnetic resonance spectroscopy assessment.

Skeletal muscle metabolism during exercise was compared in 5 patients with end-stage renal disease (ESRD) and 8 healthy controls, using a noninvasive technique, 31P magnetic resonance spectroscopy (MRS). After 3 months of anaemia correction with recombinant human erythropoietin (rHuEPO) these patients were re-evaluated. Maximal power achieved by the ESRD patients during a dynamic wrist flexion exercise test was 33% lower (p < 0.05) than the controls. Similarly in the ESRD group, the power at the onset of metabolic acidosis (the intracellular threshold) was 29% less than controls. The metabolic differences observed in the patients indicated a lower aerobic capacity. Three months of rHuEPO treatment resulted in a 55% increase in mean haematocrit but conferred no significant improvement in metabolic parameters at rest or during exercise. The lack of any significant changes in muscle metabolism following the correction of anaemia suggests that oxygen availability is not the exclusive limiting factor for aerobic metabolism in ESRD patients.

Insulin protects against hepatic bioenergetic deterioration induced by cancer cachexia: an in vivo 31P magnetic resonance spectroscopy study.

The bioenergetic effects of cancer cachexia on the livers of male Fischer rats inoculated with a methylcholanthrene-induced sarcoma were assessed using serial in vivo 31P magnetic resonance spectroscopy. Rats were randomized into three groups: tumor-bearing controls (n = 7); an insulin-treated group receiving 2 units/100 g body weight/day starting 21 days after implantation (n = 8); and a chronic insulin-treated group receiving insulin every day after implantation (n = 3). During the 32-day study, serial measurements of food intake, body weight, and tumor volume were taken, and 31P magnetic resonance spectroscopy analyses of the livers were conducted every 7 days after tumor implantation. Neither the short-term nor the chronic insulin treatment regimens stimulated the progress of tumor growth. However, both treatments prevented body weight loss, and the short-term insulin treatment prevented tumor-induced decrease in food intake relative to the control group. Liver bioenergetic deterioration was evaluated from the increase in the ratio of Pi to ATP obtained from the hepatic 31P magnetic resonance spectra. At day 28 postimplantation, control rats exhibited appreciable hepatic bioenergetic deterioration, i.e., a Pi/ATP ratio of 1.41 +/- 0.35 (SE), significantly higher (P < 0.05) than the Pi/ATP ratio for short-term or chronic insulin treatment groups (Pi/ATP 0.92 +/- 0.22 and 0.84 +/- 0.22, respectively) or rats before tumor implantation (Pi/ATP 0.76 +/- 0.14). This insulin-induced bioenergetic protection occurred at any given tumor burden up to at least 10%. Thus, both short-term insulin given just prior to the frank manifestations of cancer cachexia and chronic insulin treatment given throughout tumor growth ameliorated host hepatic bioenergetic deterioration without significantly stimulating tumor growth. Insulin may act by altering the host metabolism (stimulation of liver glucose uptake and utilization, decreased energy-requiring gluconeogenesis, and general protein-sparing action) at the expense of the tumor.

Pulmonary uptake of sestamibi on early post-stress images: angiographic relationships, incidence and kinetics.

Early post-stress imaging with 99Tcm-sestamibi has the potential to reveal ancillary markers of severe coronary artery disease. Lung/myocardial ratios of sestamibi were assessed after pharmacologic, exercise or combined stress, and these were compared with historical controls who were stressed similarly, but imaged with 201Tl. Forty initial patients had planar imaging and correlating angiograms; pulmonary uptake for sestamibi related to severe coronary artery stenoses when measured on immediate images, started at 4 min post-stress (P = 0.04), but had a poor relationship to angiographic findings when measured on delayed clinical images. Of 180 subsequent studies, increased pulmonary uptake of sestamibi was seen more frequently (incidence = 34%) in those with abnormal tomograms compared to those with normal tomograms (incidence = 13%, P < 0.01), but appeared less frequently than on abnormal 201Tl studies (incidence = 60%). With sequential imaging for 5 min after injection, pulmonary uptake showed a greater fall with time on sestamibi studies than on matched 201Tl studies. No consistent differences were seen among the stress modalities. As an ancillary sign of haemodynamically severe disease, increased pulmonary uptake can be seen after various stress modalities, but may be more difficult to apply with sestamibi than with thallium imaging.

Forearm P-31 nuclear magnetic resonance spectroscopy studies in oculopharyngeal muscular dystrophy.

Five siblings with autosomal dominant oculopharyngeal muscular dystrophy (OPMD) underwent P-31 Nuclear Magnetic Resonance Spectroscopy studies of forearm flexor muscles. Mean values of PCr/(PCr+Pi) in the patients were reduced (p = 0.01) and pH elevated (p = 0.02) in resting muscle when compared to controls. During exercise PCr/PCr+Pi) fell quickly to values less than controls (p less than 0.0001) despite submaximal exercise output and developed exercise-induced acidosis which exceeded that of controls (p = 0.05). Acidosis recovered slowly despite relatively normal recovery of PCr/(PCr+Pi) following exercise. Within the patient group, however, one member had normal resting, exercise and recovery values. The studies suggest that OPMD is a more widespread disorder of striated muscle than clinically appreciated. The pattern of findings observed in OPMD differs from those identified in denervation, disuse and mitochondrial myopathy.

A preliminary study of magnetic resonance relaxation times (T1 and T2) in inflammatory and degenerative synovial fluids.

Multiple synovial fluid samples from 21 patients were analysed using standard synovial analysis techniques and by nuclear magnetic resonance spectroscopy. Significant negative correlations were noted between both T1 (P less than 0.01) and T2 (P less than 0.0006) relaxation times and synovial fluid total protein. No differences in T1 or T2 relaxation times were noted in synovial fluid between 16 patients with inflammatory forms of arthritis and five patients with degenerative arthritis. In a single rheumatoid arthritis patient with concurrent staphylococcal arthritis, T1 and T2 relaxation times did not vary between the active phase and the recovery phase. The lack of any significant differences in the measured relaxation times as a function of joint condition suggest that in vivo magnetic resonance measurements of T1 or T2 for joint analysis may not reveal information of either a diagnostic or pathophysiological nature.

Post-polio fatigue: a 31P magnetic resonance spectroscopy investigation.

Changes in high energy phosphates (HEP) and intramuscular pH during exercise were measured in 17 patients with post-polio fatigue and in 28 healthy controls using 31P magnetic resonance spectroscopy (MRS). Subjects performed a dynamic hand grip exercise at low and high intensity. Mean changes in the HEP and pH showed no significant differences between the groups, although the post-polio group's response was highly variable. Six patients showed evidence of a lower lactate accumulation during the high intensity exercise when compared with controls. These data suggest that the whole body fatigue experienced by polio survivors is not related to any systemic metabolic abnormality.

Differential renal uptake of 201Tl: requirements for acquisition, display and quantification.

Renal uptake of 201Tl may have a role in screening for renal asymmetry in hypertensive patients (HP) who are referred for myocardial scintigraphy. The qualitative aspects of digitized planar images, and quantified differential renal uptake (DRU) of 201Tl were rated by comparing a simple technique (S) for outlining each kidney with an interpolative background subtracted technique (IB). These parameters were assessed in an initial series of patients by varying the length of acquisition (from 1 to 5 min), delay in acquisition (from 10 to 210 min after injection), and image preparation (nine-point smoothing). Six blinded observers rated the quality of coded images. Image quality was improved (P less than 0.01) by increasing the length of acquisition to at least 2 min, by smoothing of the images and by imaging within 2 h of 201Tl injection. Variability in quantification of DRU was suboptimal with acquisition for only 1 min and was more adversely affected with S than with IB. Clinical application of the quantitative technique was assessed in 180 HP and 32 normotensive controls. With IB, the normal range for DRU was slightly greater than for S. The two techniques were comparable in identifying abnormal cases and found 21 +/- 3% (S) and 19 +/- 3% (IB) of HP as lying outside the normal 99% confidence interval. Both quantitative techniques showed excellent agreement with renal angiography (n = 24). Furthermore, preliminary experience with surface markers and with 180 degrees tomography suggests the potential for simultaneous correction for renal depth. These data justify the use of adjunctive renal imaging during myocardial scintigraphy with 201Tl.

Coincident thresholds in intracellular phosphorylation potential and pH during progressive exercise.

Dynamic changes in intracellular phosphocreatine (PCr), inorganic phosphate (Pi), and pH in human forearm muscle were studied from rest through heavy exercise by means of a ramp exercise protocol and 31P nuclear magnetic resonance spectroscopy. Eighteen healthy volunteers performed an isotonic wrist flexion exercise of repeated contractions at a frequency of 0.5 Hz. Work rate was increased continuously (ramped) at approximately 0.13 W each minute from 0.34 to 1.5 W or until fatigue. Pi/PCr was used as an estimate of the cellular phosphorylation potential of the muscle. Exercise caused a progressive increase in Pi/PCr with an initial slow and later fast component. The transition between these components was distinct and corresponded to the onset of pH decline in all subjects. These changes in Pi/PCr and pH were best fit (P less than 0.05) by a piecewise linear regression model with a break point or threshold. Repeated ramp testing of six subjects showed that the threshold was reproducible (r = 0.98). The results of this study demonstrate the existence of an intracellular metabolic threshold and suggest that indirect threshold measures (lactate and ventilatory thresholds) may reflect events at the cellular level.

Spectroscopy of the isolated rabbit heart: effects of perfusion with oxygenated crystalloid cardioplegia at 4 degrees C and 20 degrees C.

Factors that limit survival of explanted cardiac allografts include intracellular acidosis and loss of high energy phosphates. This study was undertaken to determine if these processes could be retarded by specific interventions during organ storage and to determine the capabilities of phosphorus-31 (31P) nuclear magnetic resonance spectroscopy to monitor these intracellular changes noninvasively. Thirty-six excised rabbit hearts were studied in six groups according to the storage temperature and conditions of their perfusion: nonperfused, aerated perfusate or oxygenated perfusate, each at 4 degrees C and 20 degrees C. 31P spectra were continuously obtained starting 20 mins post explanation and continuing for at least 5 h. The resulting data were analyzed to determine metabolite concentration and intracellular pH. The phosphodiesters, inorganic phosphates and phosphomonoesters, as well as the phosphocreatine and adenosine triphosphate peaks, could be reproducibly resolved. Comparisons at 0.5, 1, 2, 3, 4, and 5 h indicated that high energy phosphates were the most quickly degraded, and intracellular acidosis progressed most rapidly in nonperfused hearts at 20 degrees C. Hearts perfused with oxygenated cardioplegic solution at 4 degrees C showed significantly prolonged preservation of high energy phosphates and delayed development of intracellular acidosis. It was concluded that continuous infusion of oxygenated cardioplegic solution improves preservation of high energy phosphates at low temperatures, and that 31P magnetic resonance spectroscopy can be used to monitor these important intracellular changes rapidly and nonivasively, permitting serial studies on the same heart. This technique substantially reduced the number of animals needed for the study (36 were used in this study rather than the 216 required by traditional techniques).

A model for in vivo serial investigation of hepatic metabolism using 31P nuclear magnetic resonance spectroscopy.

We have developed an animal model which allows serial, in vivo, evaluation of high energy phosphate metabolism in rat liver, using 31P nuclear magnetic resonance spectroscopy (MRS). In seven rats, the left lobe of the was surgically relocated into a subcutaneous position. The animals recovered quickly from the surgery and continued to thrive. Localization of the liver was obtained using simple surface coil technology. Typical MRS data acquisition times were less than 45 minutes. After the 28 days, the livers showed both normal histology and 31P metabolic measures.

An in vivo animal model to study chronic adriamycin cardiotoxicity: a P-31 nuclear magnetic resonance spectroscopy investigation.

The mechanism responsible for adriamycin induced cardiotoxicity is unknown. We have developed an in vivo rabbit model for use with P-31 nuclear magnetic resonance spectroscopy which allows serial investigations of the drug's effects on myocardial metabolism. Eleven animals were studied over a 10 week period and changes in intracellular pH and phosphate metabolites were observed. The magnitude of changes in pH and inorganic phosphate were the best indicators of the severity of the cardiomyopathy. The results are consistent with an adriamycin induced degeneration of myofibrils rather than a severe metabolic impairment.