Technetium-99m Hexamethylpropylene Amine Oxime Research Articles

Technetium-99m hexamethylpropylene amine oxime single photon emission tomography in febrile convulsions.

We report our initial experience with technetium-99m hexamethyl propylene amine oxime (99mTC-HMPAO) brain single photon emission tomography (SPET) in the investigation of 19 children presenting with febrile convulsions. Two patients with complex febrile convulsions showed focal SPET lesions contralateral to the neurological deficit. However, in 9 out of 17 patients with simple febrile convulsions, focally disturbed perfusion was shown. In 4 out of 6 patients with electroencephalogram (EEG) abnormalities on admittance, SPET revealed at least 2 focal lesions. The temporofrontal region was the one most commonly involved. The SPET findings presented here also suggest a temporal relationship with the febrile convulsions, with markedly fewer lesions if examined after 12 days. In our initial experience, perfusion SPET did not show any particular pattern helpful in the differential diagnosis of the child presenting with febrile convulsions. Physiopathologically, our findings may support the hypothesis that brain tissue is regionally more vulnerable to fever, in patients presenting with febrile convulsions.

Correlations between cerebral arterial velocities, blood flow, and delayed ischemia after subarachnoid hemorrhage.

Elevated middle cerebral erythrocyte velocities and tissue hypoperfusion have been correlated with delayed ischemia after subarachnoid hemorrhage, but few studies have compared serial arterial velocities with cerebral blood flow and neurological deficits. Serial measurements of middle cerebral velocities, using transcranial Doppler ultrasonography, were performed in 34 patients after subarachnoid hemorrhage and correlated with cerebral blood flow, measured in 20 of the 34 using single-photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime and neurological evidence of delayed ischemia. In 16 patients without delayed ischemia, eight had evidence of vasospasm (greater than 120 cm/sec), but only one of seven had hypoperfusion, suggesting that vasospasm might be more common than hypoperfusion in this group (p = 0.1). In 10 patients with delayed ischemia and a lateralizing deficit, both asymmetrical middle cerebral vasospasm (eight of nine with vasospasm) and hypoperfusion (six of six studied) were concordant with the clinically ischemic hemisphere (p less than 0.05). Vasospasm occurred with nonlateralized delayed ischemia in seven of eight patients and with hypoperfusion in five of six, affecting the anterior cerebral territory in three. Concordant vasospasm and hypoperfusion were most often present in patients with delayed ischemia and lateralizing neurological deficits. Discordant results reflect inherent limitations and the different levels of the circulation monitored by the two techniques.

Cortical perfusion response to an electrical stimulation of the auditory nerve in profoundly deaf patients: study with technetium-99m hexamethylpropylene amine oxime single photon emission tomography.

Brain activation procedures associated with single photon emission tomography (SPET) have recently been developed in healthy controls and diseased patients in order to help in their diagnosis and treatment. We investigated the effects of a promontory test (PT) on the cerebral distribution of technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) in 7 profoundly deaf patients, 6 PT+ and one PT-. The count variation in the temporal lobe was calculated on 6 coronal slices using the ratio (Rstimulation-Rdeprivation)/Rdeprivation where R = counts in the temporal lobe/whole-brain count. A count increase in the temporal lobe was observed in all patients and was higher in all patients with PT+ than in the patient with PT-. The problems of head positioning and resolution of the system were taken into account, and we considered that the maximal count increment was related to the auditory cortex response to the stimulus. Further clinical investigations with high-resolution systems have to be performed in order to validate this presurgery test in cochlear implant assessment.

A quantitative approach to technetium-99m hexamethylpropylene amine oxime.

A non-invasive, simple method for the quantitative evaluation of brain perfusion is presented using intravenous radionuclide angiography with technetium-99m hexamethylpropylene amine oxime (99mTc-HM-PAO). Graphical analysis was employed for the evaluation of the unidirectional influx constant (ku) of the tracer from the blood to the brain. The ku values were standardized to provide objective and comparable values, brain perfusion indices (BPI), among studied subjects by setting the ratio of ROIbrain size to ROIaorta size at 10. The whole-brain BPI values for the normal control subjects showed a significant negative correlation with advancing age (r = -0.632, P = 0.0204, n = 13). The mean of the whole-brain BPI of 7.0 (SD = 1.4) in 20 patients with cerebrovascular disorders was significantly lower than that of 10.6 (SD = 1.5) in 13 normal control subjects. The BPI measurements showed only minimal intra- and interobserver variability. Changes of the ratio of ROIaorta size and ROIbrain size did not significantly influence the BPI values. Hemispherical BPI values in 19 subjects (n = 38) showed highly significant correlations with the hemispherical mean cerebral blood flow values obtained from Xenon-133 single photon emission tomography (SPET) (r = 0.926, P = 0.0001 for the early picture method and r = 0.932, P = 0.0001 for the sequential picture method). This technique is easy to apply as an adjunct to SPET and may be helpful in the quantitative evaluation of brain perfusion in routine clinical studies.

Comparison of SPECT, EEG, CT, MRI, and pathology in partial epilepsy

Twenty children with partial epilepsy who had surgery between the ages of 4 1 2 months and 18 years were studied preoperatively with electroencephalography (EEG), computed tomography (CT), and technetium-99m hexamethylpropyleneamineoxime 99mTc-HmPAO single photon emission computed tomography (SPECT; 20 interictal, 4 postictal). Fourteen had magnetic resonance imaging (MRI). All had an epileptiform focus (12 unilateral, 8 predominantly unilateral) on EEG. The combination of interictal and postictal regional cerebral blood flow (rCBF) abnormalities alone correlated with EEG foci in 16 of 20 patients. Interictal rCBF abnormalities correlated with EEG foci in 14 of 20. CT findings correlated with EEG foci in 14 of 20. MRI findings correlated with EEG foci in 13 of 14. Pathology demonstrated tumor in 6, cortical dysplasia in 4, mesial temporal sclerosis in 3, Sturge-Weber in 2, cavernous hemangioma in 1, Rasmussen encephalitis in 1, porencephalic cyst and gliosis in 1, and cysts found at surgery (but normal histology) in 2. Interictal and postictal SPECT, EEG foci, and CT findings each correlated with the pathology site in 17, 19, and 15 patients, respectively. MRI correlated with pathology site in 13 of 14 patients. Postictal and interictal abnormalities of rCBF correlated with EEG and pathology as frequently as CT. In 5 patients with normal CT scans and in 1 with a normal MRI, postictal and interictal rCBF correlated with EEG and pathology results; however, these 6 patients all had abnormalities on CT or MRI. SPECT, therefore, may be considered a valuable additional diagnostic procedure in the evaluation of epilepsy surgery candidates in that it adds to the evidence of abnormality at the involved site. EEG findings and structural neuroradiologic abnormalities, however, most influenced surgical decisions in this series.

Perfusion imaging of pancreas allografts using technetium-99m hexamethyl propylene amine oxime.

The vascular integrity and major changes in perfusion can be determined by visual interpretation of radionuclide flow studies. We studied the potential of a new radiopharmaceutical technetium-99m hexamethyl propylene amine oxime (99mTc-HMPAO) in the particular setting of pancreas transplantation. Perfusion was measured by perfusion indices (PI). Changes in graft perfusion were estimated by three independent observers. A predefined scale from 0 to 4 was used, with 0 representing no visualisation of the graft and 4 denoting sharp countour delineation and distinct demarcation from the background. In order to investigate the relation between perfusion of the pancreas graft and its exocrine function, we measured the amylase excretion rate (AER) in the urine, expressed in units per hour. It is concluded that 99mTc-HMPAO is a suitable radiopharmaceutical for pancreas allograft imaging. For the assessment of the vascular integrity in the direct postoperative period, the scintigram is very reliable. Although a correlation between exocrine function of the graft and the perfusion score was not established, it is possible to make a clear sorting of AER measurements into different groups.

Technetium-99m HM-PAO SPECT in patients with delayed neurologic sequelae after carbon monoxide poisoning.

We used single photon emission computed tomography (SPECT) with technetium-99m hexamethylpropylene amine oxime (99mTc-HM-PAO) in 14 studies on 6 patients with delayed neurologic sequelae from carbon monoxide (CO) poisoning to determine whether any changes in cerebral blood flow could be correlated with clinical or computed tomographic evidence of delayed deficits. Among the six initial CT brain scans, two showed low density of both basal ganglia and two showed decreased density of the cerebral white matter. There was no correlation between the clinical outcome and the findings of the follow-up CT brain scans. Of the two SPECTS with 99mTc-HM-PAO performed during acute anoxic insult, one showed focal hypoperfusion which appeared 20 days prior to the onset of delayed neurologic sequelae after CO poisoning. Seven SPECTs in the six patients performing the delayed phase showed diffuse patched patterns of hypoperfusion which improved on follow-up images. There was good correlation between the clinical outcome and the findings of the 99mTc-HM-PAO SPECT. In preliminary conclusion, 9Tc-HM-PAO brain SPECT can be used for predicting or evaluating the outcome of delayed neurologic sequelae after CO poisoning. Cerebral vascular changes may be the possible cause of hypoperfusion in patients with CO poisoning.

Acutely administered haloperidol-induced pattern changes of regional cerebral blood flow in schizophrenics. Observation from subtraction of brain imaging with single photon emission computed tomography using technetium-99m hexamethyl-propyleneamine oxime.

Changes in regional cerebral blood flow in brain images with single photon emission computed tomography using technetium-99m hexamethyl-propyleneamine oxime before and after intramuscular injection of haloperidol (0.08 mg/kg) were studied in 5 medicated subjects in their twenties, consisting of 5 schizophrenics and 1 patient with histrionic personality disorder, by a subtraction method of brain images. The haloperidol injection induced two types of perfusion pattern change; in 2 of the schizophrenics, a relative hypoperfusion in the frontal lobes in the images prior to injection was converted to a relative hyperperfusion. In the other 3 schizophrenics and in the patient with histrionic personality disorder, the slight left hemispheric dominance was changed to a marked right hemispheric dominance. The results indicate that haloperidol affects perfusion patterns in schizophrenics.

HM-PAO spect in head trauma.

Single Photon Emission Computed Tomography (SPECT) after intravenous administration of Technetium-99m hexamethylpropylene-amine oxime (Tc-99m HM-PAO) makes possible the evaluation of cerebral perfusion. We have been assessing the diagnostic accuracy of SPECT in some groups of head trauma patients: the preliminary results of this study are presented. Fourteen patients have been selected, all of them showing some kind of focal neurological deficit; the Computed Tomography (CT) and Nuclear Magnetic Resonance (NMR) were normal, or showed lesions that could not be responsible for the neurological deficits. In all of the patients Tc-99m HM-PAO SPECT has been performed, showing changes in cerebral perfusion in areas correlated with the abnormalities elicited on clinical examination. These results show that Tc-99m HM-PAO SPECT is a better technique than CT or NMR in demonstrating the organic basis of some neurological deficits observed after head trauma.

Increment of brain temporal perfusion during auditory stimulation

A study on the dynamic exploration of the auditory pathway is presented, in which technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (SPET) was used in volunteers with normal hearing. Changes in 99mTc-HMPAO distribution were calculated using a region of interest/whole-brain count ratio. The results showed a temporal perfusion increment of 17% (right) and 19% (left) during tonal supraliminar stimulation, which was significantly different from the control ROI. Sensitivity tests for the method were requested before any clinical application.

Accumulation of leucocytes labelled with technetium-99m hexamethylpropylene amine oxime in malignant abdominal tumours

A total of 343 leucocyte scans labelled with technetium-99m hexamethylpropylene amine oxime were reviewed that had been performed in 338 patients suspected of having abdominal infection or inflammation. There was uptake by malignant abdominal tumours in 10 cases (2.9%), which represents 62.5% of known malignancies at the time of the scintigram. Accumulation was seen in 8 patients with adenocarcinoma of the colon associated with a secondary infection in the tumour or pericolic inflammation. A large tumour that had spread beyond the bowel wall was related to a positive scintigram. Accumulation was also found twice in a malignant fibrous histiocytoma in which bleeding and an inflammatory reaction to necrosis were probably responsible for the uptake. The relevant treatment was delayed for 2 weeks-2 months in 4 patients with adenocarcinoma of the colon in whom the positive uptake was regarded as confirmation of the clinically suspected acute diverticulitis.

Effect of Central Cholinergic Stimulation on Regional Cerebral Blood Flow in Alzheimer's Disease

Patients with Alzheimer disease (AD) had reduced regional cerebral blood flow (rCBF) in the posterior parietotemporal region compared with controls, as determined with technetium-99m hexamethyl propyleneamine oxime and single photon emission tomography. Central cholinergic stimulation with physostigmine produced a focal increase in rCBF in the posterior parietotemporal region in the patients with AD but not in controls.

Delivery of propellant soluble drug from a metered dose inhaler.

The deposition of particulate suspensions delivered from a metered dose inhaler has been investigated extensively. The distribution of propellant, delivered from a metered dose inhaler, was studied by radiolabelling it with technetium-99m hexamethylpropyleneamine oxime. Andersen sampler measurements indicated that half of the dose was associated with particles in the size range 0.5-5 microns diameter. The preparation was administered to healthy subjects by inhalation and deposition was monitored with a gamma camera. Each lung image was divided into an inner, mid, and peripheral zone. The effects on deposition of varying the size of the delivery orifice (0.46, 0.61, and 0.76 mm internal diameters) and the effect of attaching a spacer were assessed. Lung deposition was independent of the orifice size within the actuator. Without the spacer the average dose deposited in the lungs was 39%, with 15% penetrating into the peripheral part of the lungs. Attachment of the spacer to the mouth-piece increased the mean lung deposition to 57% and reduced oropharyngeal deposition. The study has shown that propellant soluble drugs can be delivered efficiently to the lungs from a metered dose inhaler.

Mapping the distribution of amobarbital sodium in the intracarotid Wada test by use of Tc-99m HMPAO with SPECT.

The intracarotid amobarbital sodium, or Wada, test has been used to localize speech and memory function prior to surgical treatment of temporal lobe seizures. The authors mixed technetium-99m hexamethyl-propyleneamine oxime (HMPAO) with amobarbital sodium and injected the mixture in 25 patients with epilepsy. Single photon emission computed tomography (SPECT) of the brain was then performed to determine intracerebral distribution of the amobarbital sodium. Results of SPECT were compared with those of conventional and digital subtraction angiography (DSA). The distribution of Tc-99m HMPAO and, presumably, amobarbital sodium varied from patient to patient. SPECT revealed a statistically different distribution from that predicted with conventional angiography. The distribution also often differed from that of DSA, although the difference was not significant. SPECT revealed infrequent delivery to mesial temporal lobe structures. This emphasizes the need for caution in the use of the intracarotid amobarbital sodium test to predict the outcome of removal of these areas.

Single-Photon Emission Computed Tomography in Distal Field Hypoperfusion

To assess the ability of technetium-99m hexamethylpropyleneamineoxime single-photon emission computed tomography (SPECT) imaging to differentiate distal field hypoperfusion from other stroke mechanisms, 24 patients with acute cerebral ischemia were studied. SPECT scans were read by two physicians according to a preestablished set of criteria for distal field hypoperfusion. SPECT patterns read as "probable" or "definite" for distal field hypoperfusion were found in 42% (10/24); of these, 80% (8/10) had ipsilateral carotid occlusion or high-grade stenosis. Severe carotid stenosis was found in 43% (6/14) with SPECT scans negative for distal field hypoperfusion (Fisher exact test [1-tailed] p = 0.0796). The results suggest that a distal field hypoperfusion pattern on SPECT may identify patients with hemodynamically significant large vessel disease.

Assessment of regional cerebral blood flow (rCBF) in ischemic stroke using Tc-99m HMPAO SPECT: comparison with CT and MR findings

To assess the regional cerebral blood flow (rCBF) in ischemic stroke, we analyzed the findings of single photon emission computed tomography (SPECT) using technetium-99m hexamethyl propyleneamine oxime (Tc-99m HMPAO). The SPECT images revealed abnormal areas of decreased perfusion in 29 out of 31 subjects (93.5%), which represented a higher detection rate than those for CT and MR (89.5%, respectively). Also, the areas of decreased perfusion were frequently larger than the lesions on CT and MR. Areas of decreased perfusion remote from the CT/MR lesions were found in 10 patients, including 8 with crossed cerebellar diaschisis (CCD). Thus, studies of rCBF by Tc-99m HMPAO SPECT can be useful in the assessment of ischemic stroke.

Effect of Therapy with Oxygen under High Pressure on Regional Cerebral Blood Flow in the Interval Form of Carbon Monoxide Poisoning: Observation from Subtraction of Technetium-99m HMPAO SPECT Brain Imaging

Changes in brain images with single photon emission computed tomography (SPECT) using 99mTc hexamethylpropyleneamine oxime (HMPAO) before and after therapy with oxygen under high pressure (OHP) were measured in a 66-year-old man with the interval form of carbon monoxide (CO) poisoning by a new technique, i.e., subtraction of brain images. This study was performed 187 days after acute CO poisoning, in a state of chronic akinetic mutism that followed a lucid interval. A diffuse, but frontal-dominant, hypoperfusion pattern involving both the gray and white matter was observed in the pre-OHP SPECT image. After OHP, regional cerebral blood flow increased in both the gray and white matter and markedly increased in the frontal cortical regions. The present finding suggests that OHP is effective against the chronic state of the interval form of CO poisoning.

Evaluation of primary lung carcinoma using technetium 99m-hexamethylpropylene amine oxime: preliminary clinical experience

99mTc-labelled hexamethylpropylene amine oxime (HMPAO) is a lipophilic compound with a neutral charge which reflects tumor blood flow and has been previously investigated to estimate brain blood flow. In this study, we attempted to use 99mTc-HMPAO for the evaluation of 18 patients with histologically proven primary lung carcinoma. The eight surgical specimens revealed that viable carcinoma cells were present when the 99mTc-HMPAO accumulated in the tumor, however, extensive tumor necrosis was observed when defective or ring like uptake was seen in the tumor. Qualitative study revealed that when perfusion defects were observed corresponding to the tumor, the possibility of squamous cell carcinoma or large cell carcinoma was high instead of adenocarcinoma. Quantitative analysis revealed that the uptake ratio was statistically different between adenocarcinoma (1.6 +/- 0.1) and squamous cell carcinoma (1.2 +/- 0.4) (P less than 0.05), between squamous cell carcinoma and large cell carcinoma (0.9 +/- 0.1) (P less than 0.05), and also between adenocarcinoma and large cell carcinoma (P less than 0.01). In conclusion, 99mTc-HMPAO may be useful for the evaluation of patients with primary lung carcinoma.

Recent advances and future projections in clinical radionuclide imaging

Since the almost simultaneous development of technetium-99m and invention of the gamma camera in the 1960s, nuclear medicine has made great strides. It is largely a physiological imaging modality, so a thorough grounding in physiology is essential for aspiring nuclear physicians. In contrast, computed tomography (CT), ultrasound, magnetic resonance imaging (MRI) and special radiographic techniques, like angiography, currently provide largely anatomical information. Advances in nuclear medicine can be subdivided into seven areas: new synthetic radiopharmaceuticals, new radiolabelled biological agents, cell labelling, new singlephoton- emitting radionuclides, new approaches using radiopharmaceuticals that are already well established, positron emission tomography (PET), and physics and instrumentation. The important developments in radiopharmaceuticals have had the common aim of replacing well-established agents labelled with radionuclides other than technetium-99m with agents that can be labelled with technetium-99m and which have similar pharmacokinetics. They include technetium-99m hexamethylpropyleneamine oxime (HMPAO), which will replace iodine-123 labelled amphetamines (themselves relatively new) for imaging brain perfusion, and also partly replace the indium-111 complexes for imaging inflammation. Others are mercaptoacetyltriglycine (MAG-3) which should replace radioiodinated hippuran for renography, the isonitriles which may replace thallium-201 for myocardial perfusion imaging, and the “pseudo-gases”, such as technegas, which may replace krypton-81m for routine ventilation imaging. The need for these technetium-99m radiopharmaceuticals is due not so much to their superior pharmacokinetics (where, in fact, they are generally somewhat inferior to their non-technetium counterparts) but to considerations of convenience, camera design and image resolution, dosimetry, and ultimately cost; although, at present, they are expensive.

Effect of central cholinergic stimulation on regional cerebral blood flow in Alzheimer disease

Patients with Alzheimer disease (AD) had reduced regional cerebral blood flow (rCBF) in the posterior parietotemporal region compared with controls, as determined with technetium-99m hexamethyl propyleneamine oxime and single photon emission tomography. Central cholinergic stimulation with physostigmine produced a focal increase in rCBF in the posterior parietotemporal region in the patients with AD but not in controls.