Feasibility and safety of endoscopic evaluation of gastric emptying.

BACKGROUND AND STUDY AIMS: Scintigraphy is the currently accepted method for evaluation of gastric emptying. Although quantitative, this method is complicated, time-consuming, and costly. If a simple endoscopic technique was available for those instances when quantification of an emptying abnormality is not needed, the same clinical information could be obtained in less time and with resource savings. Our aims in this study were therefore to assess the technical feasibility, tolerability, and safety of unsedated transnasal esophagogastroscopy (T-EG) as a technique for qualitative assessment of gastric emptying. METHODS: The study was done in two phases. In the first phase, 18 volunteers (ten men, eight women) underwent T-EG at 4 hours, 5 hours, or 6 hours after ingestion of a standard meal used for scintigraphic evaluation of gastric emptying without radiolabeling. In the second phase, ten volunteers underwent T-EG after scintigraphic imaging had demonstrated complete gastric emptying. RESULTS: Subjects in both phases tolerated the procedure well and completed the study. In the first phase, 13 of 15 volunteers exhibited complete gastric emptying at 6 hours (87%), while two (13%) revealed some particulate matter in the stomach at that time. In the second phase, one of the ten volunteers exhibited a small amount of solid food residue in the stomach despite documentation of scintigraphic complete emptying. CONCLUSIONS: Evaluation of gastric emptying by unsedated T-EG is both feasible and safe. In healthy, asymptomatic individuals, complete gastric emptying of solid food may take as long as 6 hours.

Acute effect of clonidine on gastric emptying in patients with diabetic gastropathy and controls.

BACKGROUND: The treatments available for diabetic gastropathy are frequently ineffective. Clinical observations suggest that clonidine, an a-2 adrenergic agonist, may improve diabetic gastropathy symptoms. AIMS: To establish whether a single oral dose of clonidine alters the gastric emptying of a solid meal in 10 patients with diabetic gastropathy and their matched controls. A secondary goal was to compare two methods of analysis of the data from gastric emptying studies. METHODS: Clonidine, 0.3 mg, or a matched placebo were administered orally in a double-blind fashion. RESULTS: Only three of the 10 patients showed an increased gastric residual volume. Gastric emptying rates were comparable in patients and controls. Clonidine had no significant effect on gastric emptying in the controls but increased t1/2 values in the patient group. This effect just reached statistical significance only when calculated by the power exponential method (P=0.05 but not by the linear component model. CONCLUSIONS: Delayed gastric emptying is not an invariable characteristic of symptomatic diabetic gastropathy. Clonidine, given as a single dose of 0.3 mg orally, has no gastric prokinetic effects. It may act on gastric afferent innervation or, more likely, at a central site to reduce nausea and vomiting. The analysis of gastric emptying data by the power exponential and the two linear component methods yields equivalent results.

Single photon emission computerized tomography (SPECT) in detecting neurodegeneration in Huntington's disease.

Single photon emission computerized tomography (SPECT) studies were performed on 34 manifest Huntington's disease (HD) patients at various stages of clinical pathology ranging from early chorea to late dystonia with or without signs of dementia and 12 pre-symptomatic patients with abnormal terminal CAG expansions. Thirty HD patients with obvious clinical signs and seven pre-symptomatic patients without signs or symptoms of HD displayed selective caudate hypoperfusion by direct visual inspection. Such qualitative, selective striatal hypoperfusion patterns can be indicative of early and persistent metabolic changes in striatal neuropathology. SPECT studies can be useful in documenting early pre-clinical changes in patients with abnormal terminal CAG expansions and in confirming the presence of caudate pathology in patients with clinical signs of HD.

Biodistribution of 99Tcm-labelled 5-thio-D-glucose.

We studied the biodistribution and tumour localization of 99Tcm-labelled-5-thio-D-glucose (99Tcm-TG). 5-Thio-D-glucose was labelled with 99Tcm by direct stannous ion reduction. The biodistribution of 99Tcm-TG was investigated in normal rabbits and in mice bearing experimental tumours. In rabbits, the plasma and clearance of 99Tcm-TG was 14.5 +/- 2.0 and 11.3 +/- 3.0 ml.min-1 respectively. Urinary excretion at 1 h was 53 +/- 5%. 99Tcm-TG was injected intravenously in mice bearing MC26 colon carcinoma and tissue samples were analysed by gamma scintillation counting at various times. Uptake of 99Tcm-TG in tumour at 1 and 3 h was 1.6 +/- 0.3% and 1.2 +/- 0.3%; the tumour to muscle ratios were 2.7:1 and 4:1 respectively. The autoradiographic biodistribution of 99Tcm-TG in MX-1 human breast xenografted nude mice showed more persistent tumour uptake of 99Tcm-TG than 14C-2-deoxyglucose (14C-DG). 99Tcm-TG accumulated in the centre of the tumours; 14C-DG was decreased in this central region probably because of zones of infarction on necrosis. The discordance between the tumour uptake of 99Tcm-TG and 14C-DG indicates that 99Tcm-TG does not act like a glucose analog, suggesting 99Tcm-TG avidity for zones of infarction or necrosis. The further study of 99Tcm-TG in tumours and ischaemic injury is warranted.

SPET and three-phase planar bone scintigraphy in adult patients with chronic low back pain.

Among adults, low back pain (LBP) persisting for more than 3 months is a common complaint. A variety of imaging modalities including bone scintigraphy have been recommended as appropriate for the investigation of chronic LBP, even when there is no reason to suspect that the pain is due to tumour, infection or inflammatory arthritis. In this chronic LBP population, the diagnostic benefit of bone SPET, together with planar flow study, blood pool and delayed three-phase imaging, was assessed, Altogether, 2108 consecutive adult patients were entered into the chronic LBP bone scintigraphy database. Retrospective exclusion of patients with a history of tumour, infection or inflammatory arthritis reduced the population to 1390, of whom 916 underwent a lumbosacral spine flow study and blood pool imaging in addition to planar and SPET bone scintigraphy. The diagnostic benefit of these imaging studies was tabulated and compared. In addition, a retrospective chart review of the patients with renal and other soft tissue abnormalities identified by a flow study and blood pool imaging was undertaken with a view to documenting any changes in treatment planning over the 6 months following the nuclear medicine studies. Of the lumbosacral spine abnormalities, 44.1% were seen equally well on planar and SPET images, 24.0% better on SPET, 31.4% only seen on SPET, and 0.4% only seen on planar imaging. The distribution of abnormalities identified on SPET images in the lumbar spine was divided between vertebral bodies (36.1%), lamina or pedicles (which included frequent sites of increased uptake in the articular facets and pars interarticularis) (53.8%), spinous processes (8.7%) and transverse processes (1.3%). For the flow study and blood pool imaging, there was a 16.7% rate of positive studies. However, there were no documented changes in treatment planning because of these positive findings. In conclusion, when used to examine adult patients with chronic LBP, SPET detects significantly more scintigraphic abnormalities than planar imaging. The addition of a flow study and blood pool imaging as part of these LBP examinations results in a significant benefit. However, the clinical utility of such flow study and blood pool imaging studies cannot be confirmed.

Detection of osteomyelitis in the neuropathic foot: nuclear medicine, MRI and conventional radiography.

The diagnostic efficacy of (1) combined three-phase bone scintigraphy and In-111 labeled WBC scintigraphy (Bone/WBC), (2) MRI, and (3) conventional radiography in detecting osteomyelitis of the neuropathic foot was compared. Conventional radiography was comparable to MRI for detection of osteomyelitis. MRI best depicted the presence of osteomyelitis in the forefoot. Particularly in the setting of Charcot joints, Bone/WBC was more specific than conventional radiography or MRI.

Radionuclide therapy for palliation of pain due to osteoblastic metastases.

Beta-emitting, bone-seeking radiopharmaceuticals, administered systemically, represent a good alternative or adjuvant to external beam radiotherapy for palliation of painful osteoblastic bone metastases. The most frequently used radiopharmaceutical for this purpose is strontium 89, followed by samarium 153 ethylenediaminetetramethylene phosphonate, and infrequently phosphorus 32 orthophosphate. Prior to consideration for radionuclide therapy, recent bone scans should be evaluated in order to determine if the patient has painful osteoblastic lesions likely to respond to therapy. Approximately 70% of patients with prostate and breast cancer will have a reduction in pain in response to radionuclide therapy, beginning within 2 to 4 weeks and lasting between 2 and 6 months. Patients who are expected to live 3 or more months are more likely to benefit than patients with shorter duration life expectancy. Hematosuppression is the chief side effect of radionuclide therapy, with leukopenia and thrombocytopenia more likely to be clinically significant than anemia. Relative contraindications for treatment include osteolytic lesions, pending spinal cord compression or pathologic fracture, preexisting severe myelosuppression, urinary incontinence, inability to follow radiation safety precautions, and severe renal insufficiency.

Evaluation of 99Tcm-bicisate as a renal imaging agent.

99Tcm-bicisate (99Tcm-ECD), often used as a brain perfusion agent, is rapidly converted following intravenous injection to the polar monoacid (99Tcm-ECM) and diacid (99Tcm-EC) metabolites. Such polar metabolites, which are eliminated principally by renal clearance, are potential renal imaging agents. In this study, 99Tcm-ECD was compared for the first time with 99Tcm-EC, 99Tcm-mercaptoacetyltriglycine (99Tcm-MAG3) and 131I-orthoiodohippurate (OIH) as renal imaging agents in rabbits. Whole-body images and renograms were obtained for all three of the 99Tcm agents, and pharmacokinetic parameters including plasma and urinary clearance were studied for all four agents. The plasma clearance of 99Tcm-EC (37 ml min-1) was slower than that of 99Tcm-ECD (51 ml min-1), which could be accounted for by the higher liver uptake of 99Tcm-ECD. The urinary clearance of 99Tcm-ECD (35 ml min-1), 99Tcm-EC (34 ml min-1) and 99Tcm-MAG3 (39 ml min-1) was similar. The renal images obtained with 99Tcm-ECD were comparable to those for 99Tcm-MAG3 and 99Tcm-EC. However, liver uptake was more prominent with 99Tcm-ECD than with the other agents. The 99Tcm-ECD renogram curves showed a prolonged decrease in renal activity compared to both 99Tcm-EC and 99Tcm-MAG3. In potential human studies, the relatively high liver uptake of 99Tcm-ECD superimposed on right renal activity may be a limitation. Therefore, we conclude that 99Tcm-ECD is less favourable when compared to existing renal agents due to its high extrarenal uptake and renal kinetics.

Evaluation of 99Tc(m)-ECD as a white blood cell labelling agent.

99Tc(m)-ECD is a new agent for perfusion brain imaging. Its brain retention is attributed to the enzymatic conversion of lipophilic 99Tc(m)-ECD to polar monoacid and diacid derivatives. Based on its proposed mechanism of retention in the brain, labelling of white blood cells (WBC) with 99Tc(m)-ECD has been studied at our laboratory. A labelling efficiency of 42% was achieved by incubating WBC with 99Tc(m)-ECD in phosphate buffered saline medium for 30 min. There was a washout of 50% of the radioactivity from the cells in 1 h, which might contribute to increased background in potential human studies. However, rapid urinary elimination of the radioactivity is expected to deal with this problem due to the rapid in vivo conversion of the parent compound to polar metabolites. 99Tc(m)-ECD appears to be a promising agent for labelling WBC. Furthermore, already prepared multidose 99Tc(m)-ECD may be used for either brain perfusion imaging or WBC labelling.

Diagnostic bone scanning in oncology.

Over the last several decades bone scanning has been used extensively in the evaluation of oncology patients to detect bone involvement. It can provide information about disease location, prognosis, and the effect of therapy. Bone scanning offers the advantages of whole body evaluation and the detection of lesions earlier than other techniques. However, as newer diagnostic tools become available, indications for bone scanning must be revised and the results combined with these other tests in order to provide optimum patient care. Advances in instrumentation and the subsequent improvement in image quality have allowed nuclear medicine physicians to provide more accurate bone scan interpretations. By optimizing image acquisition, it is often possible to determine lesion characteristics, which are more likely to represent malignancy. Knowledge of disease pathophysiology and other specific properties of the patient's primary tumor, along with subsequent correlation of scan abnormalities to patient history, physical examination, previous studies, and other radiological examinations, is essential for determining lesion significance. The differential diagnosis of a scan abnormality should also include consideration of both false normal and abnormal causes. The final interpretation should be clearly communicated to the clinician with appropriate recommendations for further evaluation. Only through careful attention to the patient, the clinician, and appropriate study acquisition parameters will bone scanning maintain its place in the evaluation of oncology patients.

Enterogastric bile reflux during technetium-99m-sestamibi cardiac imaging.

UNLABELLED: Enterogastric bile reflux (EGBR), a risk factor for both gastritis and esophagitis, is a potentially treatable noncoronary cause for chest pain. METHODS: To investigate the frequency of EGBR during different 99mTc-sestamibi cardiac imaging, 1405 consecutive 99mTc-sestamibi SPECT myocardial perfusion studies were reviewed. RESULTS: One hundred sixteen of the 1405 patient studies (8.3%) showed EGBR with roughly equal numbers of patients having marked (43 patients), moderate (38 patients) or minimal (35 patients) intensity of abnormal gastric activity. Two examinations showed gastroesophageal reflux of activity. EGBR was less frequent with treadmill stress testing (5.5% patients) than with pharmacologic stress testing using either dipyridamole (11% of patients) or dobutamine (9.2% of patients) (p > 0.005). EGBR also was more frequent in patients over 40 yr of age. Finally, the prevalence of upper gastrointestinal symptoms and the frequency of established upper gastrointestinal diagnoses correlated strongly with the presence and intensity of EGBR. CONCLUSION: Clarification of the full clinical significance of EGBR during 99mTc-sestamibi cardiac imaging is a topic for future research. Nonetheless, the imaging finding of EGBR may, in fact, identify a potentially treatable noncoronary cause for chest pain.

Neuroradiologic applications of central nervous system SPECT.

Single photon emission computed tomography (SPECT) of the central nervous system (CNS) has many potentially useful interventional neuroradiologic applications. CNS SPECT allows easy and safe evaluation of the collateral circulation during internal carotid balloon test occlusion. The cerebrovascular distribution of intracarotid amobarbital sodium, which is used in the Wada test, can be accurately determined with simultaneous injection of a radiopharmaceutical. Easy and safe evaluation of the extent and distribution of vasospasm associated with subarachnoid hemorrhage or cerebral angiography is also possible with CNS SPECT. Images obtained after administration of acetazolamide can be compared with baseline images to evaluate cerebrovascular reserve before carotid endarterectomy. Seizure foci can be identified if peripheral intravenous injection is performed during an ictus. Thallium-201 imaging can be used to direct stereotactic brain biopsy to check for tumor recurrence. Radiologists need to familiarize themselves and their clinical colleagues with the many uses of this imaging technique.

A high-efficiency, rapid and multi-dose procedure for white blood cell labelling with 99Tcm-HMPAO.

99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) is presently recognized as an effective radiopharmaceutical for in vitro white blood cell (WBC) labelling in addition to its widespread utility in cerebral blood flow imaging. While performing clinical studies in patients with a wide range of inflammatory diseases, the effect of the ligand and stannous ion quantity on the labelling efficiency (LE) of WBC was examined. A mean LE of 64 +/- 7% (n = 29) was achieved when the whole HMPAO kit was used for labelling. The LEs were 78 +/- 5% (n = 43), 83 +/- 3% (n = 37) and 85 +/- 5% (n = 18) when one-half, one-third and one-fifth of the lyophilized kit was used, respectively. This is in agreement with the reports of Sampson et al. and Lang et al., suggesting that the optimal formulation of the 99Tcm-HMPAO is a faction of the whole kit. Accordingly, fractionation of a freshly prepared 99Tcm-HMPAO kit into five parts for a high-efficiency WBC labelling is proposed, encouraging the more widespread use of 99Tcm-HMPAO in WBC labelling.

In-111 WBC imaging of osteomyelitis in patients with underlying bone scan abnormalities.

One hundred seven combined In-111 WBC/Tc-99m MDP scans performed on 87 patients with a high clinical suspicion of osteomyelitis were retrospectively reviewed. An 86% sensitivity and a 94% specificity for detecting osteomyelitis were found. In addition, patients were grouped into one of five clinical settings for more detailed analysis: diabetic osteoarthropathy, previous arthroplasty, fracture, overlying skin ulcer, and other etiology. Forty-seven studies were performed while patients received antibiotic therapy without loss of sensitivity for detecting osteomyelitis. Results obtained with scintigraphy compared favorably to other imaging and laboratory studies used to detect osteomyelitis. In conclusion, the combined In-111 WBC/Tc-99m MDP scan is a very sensitive and specific method to detect osteomyelitis in patients with concurrent diabetic osteoarthropathy, fracture, postoperative healing, and overlying skin ulcer. Antibiotic treatment does not appear to adversely affect the sensitivity of these scans.

Evaluation of regional cerebral blood flow in massive intracerebral calcifications.

Fahr's disease is histopathologically characterized by massive bilateral calcifications of the cerebral basal ganglia, the dentate nuclei of the cerebellum and both the cerebral and cerebellar cortices. We report a case of Fahr's disease in which a 99mTc-hexamethyl-propylenamine oxime (99mTc-HMPAO) brain SPECT study was used to evaluate regional cerebral blood flow to the calcified regions. There was markedly decreased perfusion to the basal ganglia bilaterally as well as decreased perfusion to the cerebral cortices that correlated well with the patient's clinical condition.

Normal high-resolution cerebral 99mTc-HMPAO SPECT scans in symptomatic neonates exposed to cocaine.

Vascular constriction is said to account for a variety of clinical effects of cocaine. High-resolution 99mTc-hexamethylpropylene amine oxime single photon emission computed tomographic (SPECT) scans, which measure cerebral blood flow, were used to determine whether neonatal brain perfusion deficits are present in newborns with confirmed cocaine exposure. Normal, age-appropriate SPECT scans were found in 21 babies. Conventional neuroimaging was also performed when possible. All but one of the 14 magnetic resonance imaging (MRI) scans and one computed tomographic scan were normal. One MRI showed a mild delay in myelination. All but four neonates had behavioral or electroencephalographic abnormalities, and microcephaly was found in five of 21. The normal neonatal SPECT scans contrast with findings in adult cocaine users, which typically report abnormal findings of cerebral hypoperfusion. This study identifies a unique lack of corresponding cerebral vascular pathology in symptomatic neonates. It raises the possibility that many of these children can escape significant ischemic injury.

A multi-institutional study of interobserver agreement in the evaluation of dementia with rCBF/SPET technetium-99m exametazime (HMPAO).

Although specific patterns of technetium-99m exametazime [99mTc-hexamethylpropylene amine oxime (HMPAO)] brain single-photon emission tomography (SPET) uptake have been described for patients with dementia, no multi-institutional study has evaluated interobserver agreement. Interobserver agreement for 99mTc-HMPAO brain SPET uptake patterns in 50 clinically diagnosed demented subjects from four institutions were studied. Neurologists classified these subjects as presumed Alzheimer's disease (n = 21), confirmed Alzheimer's disease (n = 10), multi-infarct dementia (n = 9), HIV-related dementia (n = 7), or "mixed" (n = 3). In addition 20 normal (five per institution) 99mTc-HMPAO studies were included in a randomized blinded evaluation by three readers each from a different institution. Readers classified the general appearance of the images in one of four categories: normal, globally decreased uptake, focal areas of decreased uptake, and patchy changes in uptake. Consensus results show a sensitivity of 72% and specificity of 79% for identifying abnormalities in scans of demented subjects. Readers also rated 99mTc-HMPAO uptake in eight designated regions in each hemisphere. Significant reader agreement (P < 0.01) for the classification by general appearance and the ratings of regional uptake was obtained. This study demonstrates that interpretation of regional cerebral blood flow/SPET images is concordant across multiple institutions and readers.

The role of single photon emission computed tomography brain imaging with 99mTc-bicisate in the localization and definition of mechanism of ischemic stroke.

99mTc-bicisate (99mTc-ECD) is a new brain perfusion imaging agent formulated from a radiochemically stable kit (Neurolite). A multicenter trial was conducted to determine the sensitivity and specificity of single photon emission computed tomography (SPECT) imaging with 99mTc-bicisate in the localization of ischemic stroke; 170 subjects were enrolled, 128 patients with stroke and 42 controls. Imaging results from 148 subjects (107 stroke patients and 41 controls) were considered evaluable. In the evaluable subjects, SPECT brain imaging with 99mTc-bicisate (21.0 +/- 2.5 mCi) was interpreted without clinical information and was compared with a final assessment using all clinical, diagnostic, and laboratory procedures except the 99mTc-bicisate SPECT results. 99mTc-bicisate was safe and well-tolerated. SPECT imaging with 99mTc-bicisate demonstrated a specificity of 98% and a sensitivity of 86% for localization of strokes (kappa, 0.75; 95% confidence interval, 0.64-0.86). Results were unchanged over time and were similar for all stroke mechanisms except for lacunar disease (sensitivity, 58%). In a secondary analysis, a normal image or small, deep (e.g., subcortical) perfusion defect was highly predictive of a lacunar mechanism. Defects involving the cortical surface were strongly associated with nonlacunar mechanisms. SPECT imaging with 99mTc-bicisate is a sensitive marker in the localization of perfusion defects associated with ischemic stroke and may assist in the determination of the underlying mechanism of a stroke.

Detection of chronic coronary artery disease: value of pharmacologically stressed, dynamically enhanced turbo-fast low-angle shot MR images.

OBJECTIVE: The potential of MR imaging for evaluating myocardial perfusion and viability may make it the imaging procedure of choice for examining patients with ischemic heart disease. Accordingly, the purpose of this study is to determine the value of pharmacologically stressed, dynamically enhanced turbo-fast low-angle shot (FLASH) MR imaging in detecting chronic coronary artery disease. SUBJECTS AND METHODS: Five patients who had coronary angiography within the past 6-12 months were included in the study. After injection of 0.56 mg/kg of dipyridamole over 4 min, a bolus of 0.05 mg/kg of gadopentetate dimeglumine and subsequently 10 mCi (370 MBq) of 99mTc-sestamibi were injected. Short-axis turbo-FLASH images were obtained before injection and immediately, 1 min, 3 min, and 5 min after the injection of contrast material. Stress single-photon emission computed tomography (SPECT) images of the heart were obtained 60 min after the 99mTc-sestamibi injection. One and a half hours after an additional 30 mCi (1110 MBq) of 99mTc-sestamibi was injected, SPECT images were obtained with patients at rest. Prospective MR imaging evaluation of these five patients was performed by radiologists who did not know any of the imaging data. The MR imaging studies were compared with the near simultaneous 99mTc-sestamibi SPECT studies and with recent coronary angiograms. RESULTS: Thirteen myocardial segments were diagnosed as abnormal when 99mTc-sestamibi SPECT was used as the gold standard (12 reversible defects and one fixed defect). Twelve segments were normal on the 99mTc-sestamibi SPECT study. With SPECT as the gold standard, prospective MR imaging had a sensitivity of 77% and a specificity of 75%, whereas retrospectively it had a sensitivity of 92% and a specificity of 75%. With recent coronary angiography as the gold standard, prospective MR imaging had a sensitivity of 81% and a specificity of 100%. The quantitative data did not improve the accuracy of the qualitative analysis. CONCLUSION: Our results suggest that accurate prospective identification of chronic coronary artery disease may be possible with dynamically enhanced, pharmacologically stressed, turbo-FLASH MR imaging. Studies of additional patients to confirm this initial impression are warranted.