Late noninvasive evaluation of cardiac performance in mildly symptomatic older patients with Ebstein's anomaly of tricuspid valve: role of radionuclide imaging.

Ten patients 8 to 54 years of age with isolated Ebstein's anomaly of the tricuspid valve were evaluated by electrocardiography, maximal exercise treadmill testing, 24 h electrocardiographic (ECG) monitoring, echocardiography and rest radionuclide imaging of the left ventricle. The patients presented after the 1st year of life and had not undergone surgical intervention. All except one were in functional class II. No patient had preexcitation on the surface ECG, but abnormal tachyarrhythmias or bradyarrhythmias were seen in five patients on 24 h ECG monitoring. Subnormal exercise performance was observed in five patients. Echocardiography demonstrated typical variable tricuspid valve displacement and paradoxic interventricular septal motion. Left ventricular end-diastolic dimensions were normal in all patients, but posterior wall motion was reduced in two. Moderate to severe tricuspid regurgitation with a Doppler jet velocity less than 2.5 m/s was demonstrated in eight patients. Left ventricular radionuclide scintigraphy revealed a subnormal ejection fraction (less than 50%) in 5 of 10 patients; these 5 had previously shown suboptimal exercise performance. The two youngest patients (less than 15 years) had no arrhythmia, normal exercise performance and normal left ventricular ejection fraction. There was no correlation between the degree of tricuspid valve displacement or regurgitation and the presence of rhythm disturbance, exercise performance or radionuclide left ventricular function. Late evaluation of patients with Ebstein's anomaly may demonstrate significant unsuspected abnormalities in cardiac rhythm, exercise performance and left ventricular function. Radionuclide scintigraphy is a useful noninvasive technique for assessing left ventricular dysfunction in these patients.

A prospective, randomised double-blind crossover study to examine the efficacy of strontium-89 in pain palliation in patients with advanced prostate cancer metastatic to bone.

The palliative efficacy of strontium-89 chloride has been evaluated in a prospective double-blind crossover study comparing it with stable strontium as placebo in 32 patients with prostate cancer metastatic to bone. Response was assessed 5 weeks after each treatment. 26 patients were evaluable. Complete pain relief was only reported following strontium-89 injection. Statistical comparison between placebo and strontium-89 showed clear evidence of a therapeutic response to strontium-89 compared with only a limited placebo effect (P less than 0.01).

Xenon-133, 127Xe, and 125Xe for lung function investigations: a dosimetric comparison.

Of the possible radionuclides of xenon, 127Xe and 125 Xe have better physical properties for lung function measurement than 133Xe. A comparison of the radiation doses for these three radionuclides has been made for a typical scintillation camera investigation. Using an exponential model for washin and washout of gas, it is shown that the specific activity-time relationship is always equal to the product of the spirometer concentration and the rebreathing period. It is concluded that of the three radionuclides 127Xe gives the lowest radiation dose during a typical lung function study.

Scintigraphic estimation of arterial and portal blood supplies to the liver.

A technique is described for the measurement of the relative magnitudes of the hepatic-artery and portal-vein components of liver perfusion, using a gamma camera and on-line computer system. This ratio is obtained from analysis of the time variation in liver activity on the first pass following bolus intravenous injection of a Tc-99m-labeled radiocolloid. The arterial and portal components are separated by their times of arrival at the liver. These arrival times are evaluated from activity time variations for spleen, left ventricle, and left kidney. Physiological validation of the technique was provided in a digestion study in which normal volunteers showed a significant increase in the portal-vein component 1 hr after a meal relative to the fasting situation. These results are compared with those from studies by other workers. The uncertainties and limitations of the technique are discussed and potential clinical uses suggested.

In vivo measurement of liver perfusion in the normal and partially hepatectomized rat using Tc-99m sulfur colloid.

A nonsacrificial technique for measurement of liver perfusion in rats using Tc-99m sulfur colloid and gamma camera with computer system is described. The results of measurement in normal rats and at various stages after partial hepatectomy are presented and are compared with results obtained by workers using other techniques. The method reported here is simpler to perform than those previously reported and has the additional advantage that frequent sequential determinations of liver perfusion can be made.

In vivo assessment of hepatic-arterial and portal-venous components of liver perfusion: concise communication.

An in vivo technique for assessment of the relative contributions of hepatic artery and portal vein to liver perfusion has been developed in the rat. Dynamic scintigrams have been obtained following i.v. bolus injection of Tc-99m sulfur colloid. Temporal separation of the arterial and venous phases has been verified by hepatic-arterial ligation and portacaval diversion. The former procedure abolishes the early arterial phase of normal uptake. Portacaval diversion similarly eliminates the delayed venous phase. Assessment of the individual components of liver perfusion is of promise in the investigation of hepatic dysfunction.

Measurement of glomerular filtration rate with technetium-99m DTPA: comparison of plasma clearance techniques.

We have compared several techniques for measuring [99mTc]DTPA plasma clearance following single injection to estimate glomerular filtration rate (GFR). Half hourly measurements of disappearance of plasma activity were used to calculate a reference GFR corrected for one-pool assumption and body surface area. Alternative methods involving (i) single blood sample, (ii) two blood samples, (iii) external detector clearance rate, and (iv) a combination of (i) and (iii) were then compared. Closest correlations were obtained with (i) two blood samples at 2 hr and 4 hr (s.e.e. 2.8 ml/min) and (i.v.) external rate constant from 2-5 hr with a blood sample at 3 hr (s.e.e. 3.0 ml/min). Correlations with single blood sample were closest at 3 hr and 4 hr postinjection (s.e.e. 5.4 and 4.5 ml/min, respectively). External detector disappearance rate constant alone was least accurate (s.e.e. greater than 10 ml. min).

Strontium-89 therapy: measurement of absorbed dose to skeletal metastases.

We report measurements of absorbed dose to vertebral metastases in ten patients referred for 89Sr therapy for disseminated prostatic carcinoma. Patients received a tracer dose of 85Sr at the time of 89Sr treatment and metastatic strontium retention was monitored scintigraphically for 6 mo. Metastatic 85Sr activity corrected for tissue attenuation was measured using the conjugate view principle, with special care taken to eliminate errors due to the selection of the metastatic region of interest. Metastatic volume was determined from high resolution CT images, and density inferred from Hounsfield number using the QCT bone mineral calibration of Genant and Cann. The mean absorbed dose was 850 rad/mCi (23 cGy/MBq) with a range from 220-2260 rad/mCi (6 to 61 cGy/MBq). The wide range found was consistent with the variation expected to arise due to differences in strontium renal plasma clearance (range 0.1-11.81/day) and extent of skeletal metastatic disease (varying from two small metastases to a superscan on [99mTc]MDP images) among the patients studied.

Radio-iodobenzylguanidine for the scintigraphic location and therapy of adrenergic tumors.

Radioiodinated meta-iodobenzylguanidine, a recently developed radiopharmaceutical, has been shown to permit safe, noninvasive, sensitive, and specific scintigraphic location of pheochromocytomas of all types. The technique is especially efficacious in the case of extraadrenal primary lesions and locally recurrent and metastatic tumors. In addition to being taken up by pheochromocytomas, meta-iodobenzylguanidine may be used to image neuroblastomas, nonfunctioning paragangliomas, and carcinoid tumors. Lesions with high 131I-meta-iodobenzylguanidine uptake may respond to treatment with large doses of this radiopharmaceutical.

The treatment of resistant neuroblastoma with 131I-mIBG: alternative methods of dose prescription.

A UK multi-centre study has been carried out to collect medical and dosimetry data from treatments with 131I-metaiodobenzylguanidine (mIBG) for patients suffering from resistant neuroblastoma. All data have been acquired in a standardised way, following strict physics and clinical protocols. The accuracy of three different methods of dose prescription was studied. The results show that the most accurate method involved the use of an initial tracer study to determine the therapeutic activity required to deliver a predetermined absorbed whole-body (WB) dose.

A comparison of dopamine and homovanillic acid excretion, as prognostic indicators in malignant phaeochromocytoma.

The urinary excretion of dopamine and its metabolite homovanillic acid (HVA) were compared in 15 patients with malignant phaeochromocytoma. Six patients with increased dopamine and HVA excretion had disseminated malignancy and the poorest prognosis. Four patients with increased urinary dopamine levels but normal HVA excretion also had widespread metastases and poor prognosis. The best prognosis was for 5 patients who had normal excretion of dopamine and HVA, and minimal disease. When dopamine and HVA excretion were considered separately, it was found that duration of survival was significantly better for patients with normal dopamine excretion than those with increased dopamine excretion (p less than 0.003). There was no significant difference in survival time between patients with normal and increased HVA excretion. In this study dopamine excretion appeared to be a more discriminating biochemical index of malignancy, prognosis and disease progression than HVA excretion.

Association of hypovolemia after subarachnoid hemorrhage with computed tomographic scan evidence of raised intracranial pressure.

Hypovolemic patients are more likely to suffer delayed cerebral ischemia and infarction after a subarachnoid hemorrhage (SAH). Prompt recognition and correction of hypovolemia may improve the outcome. We have identified computed tomographic (CT) scan findings that increase the probability of a patient presenting with hypovolemia soon after an SAH. The plasma volume (PV) of 25 patients admitted within 96 hours of an SAH was measured using radioiodinated serum albumin. The normal PVs were measured in an outpatient setting 6 months later or predicted from their total body water. Nine patients (36%) were found to be hypovolemic, defined as a fall in PV exceeding 10% of the normal PV (mean fall, 18 +/- 2%). Sixteen patients were normovolemic or hypervolemic (mean PV, +9 +/- 2%). The basal cisterns were compressed or obliterated on the CT scans of all hypovolemic patients compared with 12.5% of normovolemic patients (chi-square, 14.52; P less than 0.01). The probabilities of a patient being hypovolemic if the CT scan indicated raised intracranial pressure were high: hydrocephalus, P = 0.80; compression of the basal cisterns, P = 0.82; and compression of the basal cisterns associated with intracerebral hematoma or midline shift, P = 1.00. Patients with an SAH and radiological evidence of raised intracranial pressure should be considered at particular risk for systemic hypovolemia.

A simple method for correcting left ventricular equilibrium radionuclide angiography for the effects of arrhythmias.

A simple method of correcting equilibrium radionuclide angiographic data for the effects of arrhythmias is proposed. This involves no further acquisition time or inconvenience to the patient. This correction is necessary in patients with marked arrhythmias as the left ventricular time-activity curve (LVTAC) becomes distorted with greater sampling time in the first few frames of the LVTAC than in later frames. This will show on the LVTAC as greater counts in the first few frames and will lead to an overestimation of left ventricular ejection fraction (LVEF) and wall motion. The method proposed normalises each frame to make the contribution from a non-cardiac region constant over the cardiac cycle. Results of the correction are presented and discussed.

Deconvolution analysis of the scintillation camera renogram.

A scintillation camera with digital data store has been used to assess renal function. Analysis of the renogram by deconvolution, using an on-line digital computer, shows promise as a means of expressing renal function in terms of tubular transit times for 123I-Hippuran.

Isotope bone imaging in suspected scaphoid trauma.

The unreliability of radiological examination in excluding or confirming a suspected scaphoid fracture after carpal trauma is a well-recognised diagnostic problem. This paper explores the role of isotope bone imaging (IBI) in the early identification of carpal bone injury. Abnormal generalized uptake of activity may be seen within the carpus, possibly as a consequence of diffuse soft tissue injury, particularly if imaging is performed within 48 hours of trauma. A focal area of increased uptake related to one carpal bone is suggestive of fracture though the part which ligamentous injury, localized periosteal reaction or incomplete cortical infarction may play in the production of such radionuclide appearances is uncertain. Ninety-nine patients with suspected recent scaphoid fracture but no demonstrable abnormality on radiological examination were subjected to IBI, using 555 MBq (15 mCi) of 99Tcm methylene diphosphonate. Abnormal focal increased uptake (AFIU) was found in 47 patients, this being localized to the scaphoid bone in 26. Of these 47 cases, 19 (42%) showed subsequent radiological evidence of fracture. The results of IBI, in our experience, can only be reliably interpreted if imaging is performed at least 48 hours after injury, though in cases of fracture AFIU may persist for several years. Using this technique, the possibility of fracture can be confidently excluded in that group of patients who show no AFIU. In selected cases of carpal trauma, IBI provides a satisfactory alternative means of identifying the presence and site of localized injury within the carpus and may be used to confidently exclude those patients with non-osseous symptomatology.

Strontium-89 therapy: strontium kinetics and dosimetry in two patients treated for metastasising osteosarcoma.

We report a study of strontium kinetics in two patients who received 89Sr therapy for disseminated osteogenic sarcoma, together with estimates of absorbed dose to the principal metastases and to bone marrow. In neither patient did tumour uptake of strontium have a significant effect on whole-body retention. In one patient, whole-body strontium kinetics agreed closely with the ICRP standard model, while in the second, retention was extremely prolonged, probably due to hypertrophic osteoarthropathy. Strontium-85 scintigraphy, surface counting and high-resolution whole-body profiles agreed in showing that in both patients tumour turnover of strontium was very rapid, with a biological half-life of only a few days. Absorbed dose to tumour was found to be comparable in magnitude to the mean bone-marrow dose. We have no reason to believe that 89Sr therapy was of clinical benefit to either patient.

Strontium-89 radionuclide therapy: a dosimetric study using impulse response function analysis.

In a series of patients receiving 89Sr palliation for metastasised prostatic carcinoma, strontium renal plasma clearance was found to vary from 0.14 to 11.81 day-1, and the extent of skeletal metastatic disease seen on 99Tcm-MDP images varied from a few small metastases to a superscan. Using a numerical technique based on impulse response function (IRF) analysis, we have investigated the effect of such variation between patients on 89Sr dosimetry. The whole-body IRF, HWB(t), is defined by the deconvolution of the whole-body strontium retention function, RWB(t), with the plasma retention function, P(t). For patients with minimal metastatic bone disease we assumed HWB(t) = HO(t), where HO is the IRF derived from the International Commission on Radiological Protection model for normal strontium metabolism. The strontium plasma clearance, k, was allowed to vary, and the resulting variation of RWB(t), P(t) and absorbed dose to bone marrow calculated. By convoluting P(t,k) with the IRF measured for a discrete metastasis, the effect of varying k on tumour dose was investigated. Tumour and bone marrow dose were shown to change by a factor of three as k varied over the range observed in patients. For patients with extensive metastatic bone disease we assumed HWB(t) = (1-beta)HO(t) + beta HS(t), where HS was the IRF measured for a superscan patient and beta was a parameter reflecting the extent of skeletal metastatic disease. The effect of varying beta on tumour and bone marrow dose was investigated, and dose shown to decrease by a factor of five as beta increased from zero to unity. Impulse response function analysis was found to be a powerful and useful aid in clarifying the relationship between strontium kinetics and 89Sr dosimetry.

Strontium-89 chloride for pain palliation in prostatic skeletal malignancy.

In a multi-centre study strontium-89 was shown to be effective in relieving bone pain from prostatic carcinoma in patients who had failed conventional therapies. Of 83 patients assessed at 3 months, following the administration of a dose of at least 1.5 MBq/kg, 75% derived benefit and 22% became pain free. Symptomatic improvement usually occurred within 6 weeks and continued for between 4 and 15 months (mean 6 months). Based on the dose estimation part of this study the recommended dose of strontium-89 is 150 MBq. Toxicity was low, provided platelet levels were above 100 x 10(9) l-1 at the time of treatment. Repeat treatments with strontium-89 may be given at intervals of not less than 3 months. Strontium-89 is administered intravenously on an out-patient basis with no special radiological protection precautions.

Assessment of progression of secondary bone lesions following cancer of the breast or prostate using serial radionuclide imaging.

A serial study on 32 patients with bone metastases following cancer of the breast or prostate was performed over three years. Up to ten sets of images (average of four) per patient were obtained during this period using 99Tcm methylene diphosphonate as the radiopharmaceutical. Ninety-three paired serial images of individual lesions were qualitatively assessed for change by three physicians in nuclear medicine and the results were compared with the quantitative results from computer analysis. The reproducibility of the quantitative approach was determined by the analysis of 20 paired lesions by three physicists. It was found that quantitative changes in uptake of less than 20% between images were generally not detected by the medical observers; a change of 41% had only a 95% probability of being identified as change by the physicians. Although much more reproducible in determining changes in individual lesions, the quantitative approach was found to be inferior to the qualitative assessment of overall change in the majority of cases which involve multiple lesions. The basic assumption that uptake varies proportionally with progression of the bone lesion is discussed an is considered in some instances to be untenable. The conclusion is drawn that the determination of progression from changes of uptake in longstanding lesions is uncertain and is subsidiary in importance to the detection of new lesions.

left ventricular segmental wall motion-a comparison between equilibrium radionuclide angiography and contrast angiography.

The qualitative assessement of left ventricular wall motion using a four-point scale has been compared between left ventricular contrast angiography and equilibrium radionuclide angiography in the 30 degrees right anterior oblique projection. Analysis was carried out for five segments of the left ventricle. Four modes of analysis of equilibrium radionuclide angiography were compared and the reproducibility assessed. Overall accuracy of equilibrium radionuclide angiography compared to contrast angiography was greater than 82% to within one degree of motion. One method using a cine display, averaged 97%. We suggest that equilibrium radionuclide angiography using the cine display is the non-invasive investigation of choice in the screening of patients with suspected regional wall motion abnormalities.