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.

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.

Effect of cancer on the in vivo energy state of rat liver and skeletal muscle.

The effect of increasing tumor burden on host liver and skeletal muscle energy status was studied using P-31 nuclear magnetic resonance spectroscopy (NMR), in rats inoculated with a nonmetastasizing methylcholanthrene-induced sarcoma (TB), and compared to nontumor bearing (NTB) and pair-fed (PF) rats. During the 28-day study, serial measurements of body weight, food intake, and tumor volume were obtained. Using a 0.9-cm double-turn surface coil, weekly NMR measurements were obtained from liver and skeletal muscle. An increasing ratio of [Pi]/[ATP] was used as one measure of intracellular energy depletion. [Pi]/[ATP] in NTB rats remained constant over time at 0.78 +/- 0.10 in liver, and 0.30 +/- 0.10 in skeletal muscle. In TB rats, the [Pi]/[ATP] ratio increased significantly in liver (P = 0.00002) and skeletal muscle (P = 0.04) with increasing tumor burden. In PF rats, no significant change occurred in [Pi]/[ATP] in liver or skeletal muscle, indicating that declining food intake was not responsible for the change in [Pi]/[ATP] seen in TB rats. Surface-coil spectroscopy of liver and skeletal muscle permits serial measurement of visceral energy stores. Increasing tumor burden results in early, ongoing depletion of energy stores as reflected by increasing [Pi]/[ATP] in these organs.

Lack of significant long-term sequelae following traumatic myocardial contusion.

We assessed the possibility of long-term functional cardiac sequelae in patients who had sustained a traumatic myocardial contusion (group 1) by comparing this group with a cohort group of patients with similar traumatic injuries but exclusive of the cardiac component (group 2). More than one year following injury, patients in group 1 were qualitatively indistinguishable from patients in group 2 according to the New York Heart Association classification. Both the left and the right ventricular ejection fractions, less in group 1 than in group 2 immediately following trauma, were similar between groups during follow-up study at rest. During exercise to maximal work load at follow-up, changes in the mean right and left ventricular ejection fractions were also similar between the two patient groups. We therefore concluded that traumatic myocardial contusion to the left and/or right ventricle almost always resolves without significant functional sequelae within one year of injury.

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.

Hypophosphatemia and respiratory failure: prolonged abnormal energy metabolism demonstrated by nuclear magnetic resonance spectroscopy.

Hypophosphatemia has been shown to cause acute respiratory failure. The mechanism is believed to be due to decreased high-energy substrate availability at the cellular level leading to respiratory muscle dysfunction. However, direct measurement of these substrates has not been previously studied. A patient with hypophosphatemic respiratory failure is described in whom phosphocreatine and pH were continuously monitored using nuclear magnetic resonance spectroscopy. This revealed a defect in muscle metabolism that required several weeks to recover despite prompt correction of the serum phosphate level.

Preparation and evaluation of radioiodinated (iodophenyl)cholines and their morpholinium and piperidinium analogues as myocardial perfusion imaging agents.

A series of nine radioiodinated quaternary ammonium salts related to phenylcholine were synthesized, characterized, and radiolabeled by exchange. These compounds were evaluated as myocardial perfusion imaging agents in mice, pigs, and humans. Mice biodistribution studies showed that five of the nine compounds were taken up in the heart to the same extent as 201Tl+ at 5 min. At 60 min myocardial retention was significantly better than 201Tl+ for six of the compounds. Several of the compounds showed more favorable heart/blood and heart/liver ratios when compared to 201Tl+. Evaluation of three of the more promising compounds in pigs and humans however revealed no selective myocardial uptake.

Effect of obstructed mediastinal venous return on dynamic brain blood flow studies: Case report.

Three patients are described who had unusual isotope brain flow studies in which the injected isotope refluxed into the internal jugular vein, entered the transverse dural sinuses, and returned proximally to a variable extent through the contralateral internal jugular vein. Mediastinal flow studies revealed obstructed pathways of venous return in the upper mediastinum. One patient had lymphoma, another had had a pneumonectomy, and the third had no demonstrable disease process to explain the flow pattern. The internal jugular-cerebral system apparently permits reversal of flow in the presence of unilateral obstruction proximal to the internal jugular vein.

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.

Persistent dural cerebrospinal fluid leak shown by retrograde radionuclide myelography: case report.

Following inadvertent spinal anesthesia for delivery, a patient developed incapacitating post-lumbar puncture headache that persisted for 9 weeks. Scintigrams of the lumbar region, obtained after injection of 99mTC-human serum albumin into the cisterna magna, showed the cerebrospinal fluid leak. Blood patch repair was carried out, with immediate relief of all symptoms. Because of subsequent atypical headaches, a second cisternogram was done by the same technique. This study confirmed that there was no further dural leak, and other evidence indicated that the recurrent headache was related to functional problems.

In vivo red blood cell compatibility testing using indium-113m tropolone-labeled red blood cells.

In vivo radionuclide crossmatch is a method for identifying compatible blood for transfusion when allo- or autoantibodies preclude the use of conventional crossmatching techniques. A technique for labeling small volumes of donor red blood cells with [113mIn]tropolone is reported. The use of 113mIn minimizes the accumulation of background radioactivity and the radiation dose especially so when multiple crossmatches are performed. Labeling red cells with [113mIn]tropolone is faster and easier to perform than with other radionuclides. Consistently high labeling efficiencies are obtained and minimal 113mIn activity elutes from the labeled red blood cells. A case study involving 22 crossmatches is presented to demonstrate the technique. The radiation dose equivalent from 113mIn is significantly less than with other radionuclides that may be used to label red cells.

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.

Hepatic uptake of technetium-99m HM-PAO in a fetus.

The normal biodistribution of technetium-99m HM-PAO ([99mTc]HM-PAO) includes significant uptake in the brain, liver, and kidneys. A pregnant patient studied with [99mTc] HM-PAO to confirm brain death provided an opportunity to examine the transplacental distribution of this radio-pharmaceutical in the unborn fetus. Uptake in the fetus after transplacental delivery is almost exclusively hepatic with a small amount of biliary excretion.

Cerebral perfusion imaging with technetium-99m HM-PAO in brain death and severe central nervous system injury.

We performed 38 cerebral perfusion studies in 33 patients with brain death or with severe central nervous system injury using technetium-99m hexamethyl-propyleneamine oxime [( 99mTc]HM-PAO). Uptake by the cerebrum and/or cerebellium was present in all patients who were not clinically brain dead (ten studies) although the study was often abnormal. In those patients who were brain dead, 16/17 studies demonstrated no uptake in either the cerebrum or cerebellum. In patients suspected of brain death, but who had conditions interfering with the diagnosis the test demonstrated no uptake in 9/11 studies, confirming brain death. A radionuclide angiogram (RNA) of the head was also performed in 33/38 studies and showed complete agreement with the [99mTc]HM-PAO uptake, except in one case. We conclude that cerebral perfusion imaging with [99mTc]HM-PAO is a simple, noninvasive and reliable test to confirm brain death. By comparison with conventional technetium agents, [99mTc]HM-PAO is not dependent on the quality of the bolus injection, is easier to interpret and allows evaluation of posterior fossa blood flow.

Hemodynamic adaptation to acute myocardial contusion complicating blunt chest injury.

The immediate hemodynamic sequelae of blunt chest injury complicated by acute myocardial contusion were examined in multiply traumatized patients. Focal defects of ventricular wall motion defined by gated cardiac scintigraphy identified acute myocardial contusion in 28 of 43 patients, involving the right ventricle alone in 18 (group 1A), the left ventricle in 4 (group 1B) and both ventricles in 6 (group 1C). Qualitatively normal ventricular wall motion was found in the 15 patients (group 2). Although there was no difference between groups 1A and 2 in mean systemic oxygen transport (620 +/- 189 vs 627 +/- 105 ml/min/m2), left ventricular ejection fraction (52 +/- 14% vs 60 +/- 9%) or calculated left ventricular end-diastolic and end-diastolic and end-systolic volumes, mean right ventricular (RV) ejection fraction was significantly lower in group 1A (29 +/- 9%) than in group 2 (47 +/- 7%, p less than 0.01). Concomitantly, evidence of RV systolic dysfunction was ml/m2) but not in group 2 (RV end-systolic volume, 50 +/- 21 ml/m2, p less than 0.05). RV stroke work was similar between the groups, and RV pump function was identical by virtue of a larger RV preload in group 1A (RV end-diastolic volume 143 +/- 63 ml/m2) than in group 2 (RV end-diastolic volume 93 +/- 26 ml/m2, p less than 0.05). Thus, use of the RV Frank-Starling mechanism in patients with traumatic RV contusion maintains RV pump function at a level similar to that in traumatized patients without acute myocardial contusion.

Frequency of myocardial injury after blunt chest trauma as evaluated by radionuclide angiography.

Seventy-seven patients who had sustained multisystem trauma, including severe blunt chest injury, were prospectively evaluated to assess the frequency of associated traumatic myocardial injury. Traumatic injury to either the right or left ventricle was defined by the presence of discrete abnormalities of wall motion on electrocardiographically gated cardiac scintigraphy in patients without a clinical history of heart disease. Forty-two patients (55%) (Group 1) had focal abnormalities of wall motion; 27 involved the right ventricle, 7 the left ventricle, 7 were biventricular, and 1 involved only the septum. Both the right and left ventricular ejection fractions were significantly (p less than 0.01) lower (31 +/- 11% and 47 +/- 14%, respectively) than those in the 35 traumatized patients without wall motion abnormalities on scintigraphy (Group 2) (49 +/- 8% and 58 +/- 11%, respectively). Repeat scintigraphic examination in 32 Group 1 patients at a time remote from initial injury showed improvement or resolution of previously defined focal wall motion abnormalities in 27 of 32 patients (84%). The electrocardiogram and serum enzyme tests were insensitive indexes of traumatic myocardial injury when defined by the scintigraphic abnormalities. Thus, severe blunt chest trauma results in a higher frequency of traumatic myocardial injury than heretofore recognized, and frequently involves the anteriorly situated right ventricle.

Biventricular function in the adult respiratory distress syndrome.

We examined biventricular function in patients with the adult respiratory distress syndrome (ARDS) by a combination of invasively determined pressures and flows and concomitant radionuclide angiography. Right (RVEF) and left (LVEF) ventricular ejection fractions were measured; right and left ventricular end-diastolic (EDVI) and end-systolic (ESVI) volume indices were calculated from the respective ejection fraction and measured thermodilution stroke volume. With an increase in the outflow pressure load on the right ventricle, measured as the mean pulmonary artery pressure (PAP), the RVEF fell (Y = 66.25 -1.01X; r2 = .42; p less than .001) and both the RVEDVI (y = 13.39 + 3.66X; r2 = .33; p less than .001) and RVESVI (Y = 23.9 + 3.57X; r2 = .41; p less than .001) increased. Progressive increases in the PAP also seemed associated with a change in left ventricular end-diastolic pressure-volume relationships: without pulmonary artery hypertension (PAP less than 20 mm Hg) the mean LVEDVI was 87.2 +/- 31.3 ml/m2 (mean +/- SD) and the mean PCWP was 5.0 +/- 2.8 mm Hg; with a mean PAP exceeding 30 mm Hg, the LVEDVI remained constant (90.4 +/- 26.9 ml/m2) although the PCWP was greater than previous (18.5 +/- 5.7 mm Hg; p less than .01). Analysis of right ventricular peak-systolic pressure end-systolic volume ratios implied a concurrent depression in right ventricular contractility at high levels of PAP. However, right ventricular "pump" function to maintain an adequate left ventricular preload remained unaltered regardless of the presence of pulmonary artery hypertension.

Alveolo-capillary permeability in human septic ARDS. Effect of high-dose corticosteroid therapy.

High-dose corticosteroid therapy has been advocated as adjunctive therapy in the adult respiratory distress syndrome (ARDS). We evaluated the effect of pharmacologic doses of corticosteroid (methylprednisolone and dexamethasone) on alveolo-capillary permeability in human septic ARDS by examining the change in appearance of intravenously administered iodine 131 (131I) human serum albumin (I-HSA) into broncho-alveolar secretions, before and after corticosteroid administration. Of 19 patients examined, in 14 (group 1) the clearance of I-HSA was reduced by corticosteroid (pre, .204 +/- .08 ml;/hr; post, .096 +/- .01 ml/hr; P less than .001), while in five (group 2) it was unaffected (pre, .23 +/- .02 ml/hr; post, .215 +/- .01 ml/hr; P=NS). Group 2 patients were more severely ill than group 1 patients in that their mean intrapulmonary shunt fractions and mean pulmonary artery pressures were higher. We conclude that high-dose corticosteroid therapy may reduce alveolo-capillary permeability in human septic ARDS if used early in the course of the illness.

Assisted ventilation in patients with preexisting cardiopulmonary disease. The effect on systemic oxygen consumption, oxygen transport, and tissue perfusion variables.

We have evaluated systemic oxygen consumption (VO2), systemic oxygen transport, and tissue perfusion variables in 30 patients with preexisting cardiac and underlying pulmonary disease during continuous positive-pressure ventilation and positive end-expiratory pressure [PEEP], during intermittent mandatory ventilation (IMV and PEEP), and during spontaneous ventilation (continuous positive airway pressure [CPAP]), with end-expiratory pressure held constant during all ventilatory modes. Using radionuclide angiography together with invasive determinations of pressure and flow, we also measured left and right ventricular ejection fractions and calculated the end-systolic (ESVI) and end-diastolic (EDVI) volume indices of both ventricles. We found that oxygen transport was significantly greater during CPAP (583 +/- 172 ml/min/M2)(mean +/- SD) than during either IMV and PEEP (543 +/- 151 ml/min/sq; p less than 0.01) or CPPV and PEEP (526 +/- 159 ml/min/M2; p less than 0.01); however, we found no significant change in systemic VO2 with conversion from CPPV and PEEP to CPAP. The increase in oxygen transport was related to a greater cardiac index and, more specifically, to a higher heart rate during CPAP (CPAP, 106 +/- 16 beats per minute; CPPV and PEEP, 97 +/- 14 beats per minute) (p less than 0.01). Enhanced oxygen transport during CPAP was also associated with an increase in mixed venous oxygenation and a decrease in arterial lactate. Although neither the mean left ventricular EDVI nor ESVI changed from CPPV and PEEP to CPAP, the mean pulmonary capillary wedge pressure increased (CPPV and PEEP, 12 +/- 5 mm Hg; CPAP, 14 +/- 7 mm Hg) (p less than 0.01), suggesting the possibility of a decrease in left ventricular compliance with the spontaneous ventilatory mode. This study suggests that in the absence of ventilatory failure, spontaneous ventilation provides for better systemic oxygen transport and overall tissue perfusion than either controlled ventilation or IMV; however, this benefit of enhanced oxygen delivery with spontaneous ventilation may potentially be offset by a decrease in left ventricular compliance.

The hemodynamic effect of rapid fluid infusion in critically ill patients.

The response to a rapidly administered volume infusion (250 ml of 5% albumin over 30 minutes) was studied in 28 critically ill patients. Cardiovascular responses were assessed by means of invasive hemodynamic parameters (i.e., cardiac index [CI], central venous pressure [CVP], pulmonary artery pressure [PAP], and pulmonary capillary wedge [PCWP] pressure as well as radionuclide [RN] angiography). This allowed for the simultaneous measurement of right (RVEF) and left (LVEF) ejection fractions, and right (RVEDV) and left end-diastolic (LVEDV) and end-systolic (LVESV) volumes. Twenty patients responded (R) to volume infusion by demonstrating an increase in stroke volume. This response was secondary to an increase in LVEDV in 11 (R-1) and an increase in the LVEF in nine (R-2). Neither response was predictable before treatment. The responders also demonstrated a significant decrease in heart rate (P less than 0.05). The increased ejection fraction in some responders (R-2) was associated with a decrease in systemic vascular resistance index (SVRI) (P less than 0.05) and LVESV (P less than 0.05) suggesting a reduced afterload secondary to peripheral vasodilation concomitant on volume change. The PCWP appeared to be related more to right ventricular (RV) loading factors (i.e., CVP, RVEDV, and pulmonary vascular resistance [PVRI] [R2 = 0.85, P less than 0.005]) then to the LVEDV (P = NS). Left ventricular (LV) loading with volume infusion appeared to be dependent on both RV performance and the PVRI in some patients, since responders who increased the LVEDV (R-1) were characterized by a simultaneous increase in RV stroke work and decrease in PVRI. The response to fluid infusion in critically ill patients is complex with both increases in LVEF and LV preload contributing to its beneficial effect. Clinical assessment of LV filling pressures (PCWP) does not accurately predict the response to volume infusion and does not allow a reliable assessment of the LV preload. This is most likely due to the broad range of LV compliance characteristics noted in critically ill patients. RV function also appears to be important in the clinical response to volume challenge.