Upregulation of granulocyte CD11b (CR 3) after labelling with technetium-99m hexamethylpropylene amine oxime

Today technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) is widely used for leucocyte scintigraphy, as^99mTc-HMPAO selectively labels granulocytes in mixed leucocyte suspensions. However, the influence of cell labelling on the expression of specific adhesion proteins has not been studied before. Therefore, we investigated five patients, four of whom had established Crohn's disease. We found that leucocyte labelling with^99mTc-HMPAO induces increased expression of the glucoprotein receptor CD11b on granulocytes, but it is not clear whether this upregulation affects the functional integrity of the granulocytes.     

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-HMPAO). Graphical analysis was employed for the evaluation of the unidirectional influx constant (k _u of the tracer from the blood to the brain. The k _u values were standardized to provide objective and comparable values, brain perfusion indices (BPI), among studied subjects by setting the ratio of ROI_brain size to ROI_aorta size at 10. The wholebrain 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 wholebrain 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 ROI_aorta size and ROIbmin 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. Offprint requests to: H. Matsuda     

Uptake of technetium-99m hexamethylpropylene amine oxime labelled white cells in lymph nodes involved in non-Hodgkin's lymphoma

Radiolabelled white cell scanning is widely used to detect the presence of infection. We present a case of non-Hodgkin's lymphoma manifesting with signs and symptoms suggestive of infection, in which a technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) white cell scan demonstrated high uptake in lymph nodes involved by lymphoma. Differential cell analysis showed preferential lymphocyte labelling. The classification and management of the disease were changed accordingly. Our findings suggest that a future role for^99mTc-HMPAO labelled white cells in the assessment of disease activity of lymphoma should be investigated.     

Evaluation of dysthymic disorder with technetium-99 m hexamethylpropylene amine oxime brain single-photon emission tomography

Dysthymic disorder is a chronic disorder characterised by the presence of a depressed mood and is classified as a distinct category in DSM-IV, separately from major depression. Although brain imaging studies have been performed in major depressive disease, there have to date been no reports of such studies in dysthymic disorder. In this study 36 patients with dysthymic disorder were compared with 16 normal subjects using technetium-99m hexamethylpropylene amine oxime brain single-photon emission tomography. A relative blood flow ratio was calculated for each region of interest using the average tissue activity in the region divided by activity in the cerebellum. There were significant differences in the bilateral inferior frontal, bilateral parietal, right superior frontal and left posterior temporal regions in the patients with dysthymic disorder compared with the healthy controls. These findings support the hypothesis that the biological bases for dysthymic disorder and major depression are similar. Recognition of these regional abnormalities may have clinical utility in both the diagnosis and the treatment of dysthymic disorder. Further studies are needed to confirm our results and to assess the influence of treatment in patients with dysthymic disorder. Received 14 August and in revised form 24 October 1998     

A quantitative approach to technetium-99m ethyl cysteinate dimer: a comparison with technetium-99m hexamethylpropylene amine oxime

To develop non-invasive regional cerebral blood flow (rCBF) measurements using technetium-99m ethyl cysteinate dimer (^99mTc-ECD) and single-photon emission tomography (SPET), the same graphical analysis as was described in our previous reports using technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) was applied to time-activity data for the aortic arch and brain hemispheres after intravenous injection of^99mTc-ECD. Hemispherical brain perfusion indices (BPI) for^99mTc-ECD showed a highly significant correlation (n = 22,r = 0.935,P = 0.0001) with those for^99mTc-HMPAO in 11 patients who underwent both tracer studies. Using both linear regression line equations between^99mTc-ECD BPI and^99mTc-HMPAO BPI and between^99mTc-HMPAO BPI and mean cerebral blood flow (CBF) values obtained from a xenon-133 inhalation SPET method in a previous study,^99mTc-ECD BPI was converted to¹³³Xe CBF values (y = 2.60x + 19.8). Then raw SPET images of^99mTc-ECD were converted to rCBF maps using Lassen's correction algorithm. In this algorithm, the correction factor a was fixed to 1.5, 2.6 and infinite. In the comparison of rCBF values for^99mTc-ECD SPET with those for^99mTc-HMPAO SPET in 396 regions of interest in the aforementioned 11 patients, the fixed correction factor of 2.6 gave nearly the same rCBF values for^99mTc-ECD (50.1 ± 16.9 ml/100 g/min, mean ± SD) as for^99mTc-HMPAO (49.9 ± 17.3 ml/100 g/min). In conclusion, the same non-invasive method as has been used in^99mTc-HMPAO studies is applicable to a^99mTc-ECD study for the measurement of rCBF without any blood sampling.     

Effect of deadtime loss on quantitative measurement of cerebral blood flow with technetium-99m hexamethylpropylene amine oxime

Deadtime count loss may cause error in quantitative measurements with a gamma camera. We evaluated the effect of deadtime loss on the measurement of cerebral blood flow (CBF). Radionuclide angiography with technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) was performed in 20 patients. A reference source was placed on the periphery of the detector to monitor deadtime loss, and CBF was calculated based on the data of radionuclide angiography with and without deadtime correction. In ten patients injected with 1110 MBq of the tracer, the CBF value without correction was 9.9%±1.8% higher than that with correction. This shows that deadtime loss may cause significant overestimation. The difference between CBF values obtained with and without correction was smaller in ten patients with an injected dose of 370 MBq (3.0%±1.2%). These results suggest a substantial effect of deadtime loss on CBF as measured by radionuclide angiography and ^99mTc-HMPAO. Received 14 July and in revised form 18 July 1997     

Effects of non-linear flow and spatial orientation on technetium-99m hexamethylpropylene amine oxime single-photon emission tomography

The effects of two post-acquisition corrections on the visual and quantitative analysis of technetium-99m hexamethylpropylene amine oxime (HMPAO) single-photon emission tomography (SPET) were determined. The corrections were for: (1) the improper spatial orientation of the patient data sets, and (2) the non-linear uptake of HMPAO across the blood-brain barrier. Reorienting the SPET image data sets removed observers' uncertainty in assessment caused by suspected head tilt; however, it increased their uncertainty due to perceived subtle perfusion deficits. Applying the correction to compensate for the decrease in uptake of HMPAO in high-flow regions resulted in an increase in the number of positive assessments. In a study involving 30 patient studies, intea-observer reliability increased from 62% to 83% (average of two observers) after applying both of the corrections, while inter-observer reliability improved from 62% to 81%. Quantitative methods of analysing the images are also affected by the corrections. In an ROI-based classification scheme, the quantitative assessments of more than one-half of the images are affected by the two corrections. These results need to be considered when comparing both quantitative and visual results from different studies in which the corrections may or may not have been applied.     

Brain single-photon emission tomography with technetium-99m hexamethylpropylene amine oxime in adolescents with initial-stage schizophrenia

The objective of this study was to search for regional cerebral blood flow (rCBF) abnormalities in adolescents with initial-stage schizophrenia by means of brain single-photon emission tomography (SPET) using technetium-99m hexamethylpropylene amine oxime (HMPAO). SPET studies were performed on a homogeneous sample of 15 carefully selected adolescents with a recent diagnosis of schizophrenia, and without previous electroconvulsive or antipsychotic drug treatment. Computed tomography (CT) and electro-encephalographic (EEG) studies were performed in all patients. Qualitative and semiquantitative analysis of^99mTc-HMPAO SPET studies showed an impaired rCBF in 12 patients (80%). The most common pattern was a decreased uptake of^99mTc-HMPAO in the frontal lobes, usually in the left hemisphere. Conventional and quantitative EEG was positive in 12 (80%) and 15 (100%) patients, respectively. CT findings were positive in two patients (13%). There was a high level of concordance between SPET and EEG results and between SPET and clinical features (P>0.05). This study suggests that previously untreated patients in the first stages of schizophrenia present functional abnormalities that are revealed by brain SPET.     

Reliability of low-frequency auditory stimulation studies associated with technetium-99m hexamethylpropylene amine oxime single-photon emission tomography

Development of auditory stimulation tests associated with single-photon emission tomography (SPET) shows evidence of variations in perfusion related to the stimuli. Three brain SPET examinations with technetium-99m hexamethylpropylene amine oxime were performed on eight right-handed adults with normal hearing, the first one without stimulation and the other two associated with a 500-Hz/30-dB stimulation of the right ear. Temporal regions of interest covering auditory areas, as well as parietal ones (internal control), were drawn on three successive coronal slices. A cortico-cerebellar index R was calculated, and the variation in activity was defined for each subject using the ratio R _{poststlmulation} — R _{prestiunulation}/R _{prestimulation}. A significant increase in the temporal cortex count occurred in all subjects. This increase was bilateral, except for one subject in whom it was not significant on the right side. This result recurred during the second stimulation study. Overall the response of the left temporal cortex was stronger, although the asymmetry was not significant. The asymmetry repeated itself after each stimulation. The perfusion response is globally reliable in our study. We must ascertainhow sensitive this test is with regard to deaf adults and adults with normal hearing before extending its use to children. Correspondence to: Y.Le Scao     

A technetium-99m hexamethylpropylene amine oxime brain single-photon emission tomography study in adolescent patients with major depressive disorder

We have not encountered any brain single-photon emission tomography (SPET) study performed in adolescent depressed patients in the literature. Therefore, we used technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) brain SPET in adolescent patients with major depressive disorder (MDD) to examine the possible changes in cerebral perfusion and the possible association between perfusion indices and clinical variables. Fourteen adolescent out-patients (nine females, five males; mean±SD age: 13.11±1.43 years; range: 11–15 years) fulfilling the DSM-IV criteria for MDD and 11 age-matched healthy control subjects (six females, five males; mean±SD age: 13.80±1.60 years; range: 12–15 years) were included in the study. ⁹⁹Tc-HMPAO brain SPET was performed twice in the patient group and once in the control group. The first SPET investigation was performed under non-medicated conditions and the second was performed after depressive symptoms had subsided. A relative perfusion index (PI) was calculated as the ratio of regional cortical activity to the whole brain activity. We found significant differences between the PI values of the untreated depressed patients and those of the controls, indicating relatively reduced perfusion in the left anterofrontal and left temporal cortical areas. No significant differences in regional PI values were found between the remitted depressed patients and the controls. Our study suggests that adolescent patients with MDD may have regional cerebral blood flow deficits in frontal regions and a greater anterofrontal right-left perfusion asymmetry compared with normal subjects. The fact that these abnormalities in perfusion indices have a trend toward normal values with symptomatic improvement suggests that they may be state-dependent markers for adolescent MDD. Received 11 January and in revised form 11 February 1998     

The use of technetium-99m hexamethylpropylene amine oxime labelled white blood cells to detect subclinical inflammation of the heart after cardiopulmonary bypass in children with congenital heart disease

Ten children (6 boys and 4 girls, aged 1–9 years old) underwent operations with a cardiopulmonary bypass, and the technetium-99m hexamethylpropylene amine oxine (^99mTc-HMPAO) labelled white blood cell (WBC) heart scans were used to detect postoperative leukocyte infiltration in the hearts. The results showed that 80% (/810) of the cases had subclinical inflammation in the hearts (grading of WBC scans score 2), and a positive correlation (R = 0.77) was noted between the severity of the inflammation (grading of the WBC scans) and the duration of the cardiopulmonary bypass in the operations. Another control group (9 boys and 2 girls, aged 2–13 years old) underwent operations without a cardiopulmonary bypass, and subclinical inflammation of hearts was demonstrated in only 1 case (9%) by the ^99mTc-HMPAO labelled WBC scans (grading of WBC scans < score 2) after the operations. There was a significant difference (P < 0.001, by a Wilcoxon rank sum test) based upon the severity of the ischaemic heart damage in the two groups. In our preliminary conclusions, the ^99mTc-HMPAO labelled WBC heart scans may provide non-invasive and directly discernible evidence of subclinical inflammation in the heart due to a transient ischaemic state during a cardiopulmonary bypass, even if the clinical symptoms and signs of carditis are not apparent. Correspondence to: Chia-Hung Kao     

Noninvasive measurements of regional cerebral blood flow using technetium-99m hexamethylprophylene amine oxime

The previously reported method for quantitative measurements of whole-brain or hemispheric-brain perfusion using technetium-99m hexamethylpropylene amine oxime (HMPAO) radionuclide angiography is now further developed so that regional cerebral blood flow (rCBF) can be measured. Lassen's correction algorithm is used for the linearization of a curve-linear relationship between the radioactivity in the brain and blood flow as seen with single-photon emission tomography (SPET) images. In this algorithm, the cerebral hemisphere was chosen as the reference region and the correction factor was adapted to rCBF in the reference region. This new method of measuring CBF from SPET has been validated in 33 normal subjects and 22 patients with cerebrovascular disease. Regional CBF values in 20 brain regions of the normal subjects were in good agreement with reported values measured by other methods. Regional CBF in the frontal cortex was greater than that in the temporal, parietal or occipital cortex for the entire age range. This hyperfrontal perfusion tended to be less pronounced with advancing age. Seventeen patients with unilateral brain infarction showed significantly lower rCBF than normal subjects. The infarct core showed a low rCBF value of 11.1 ml/ 100 g/min on average. An increase in rCBF after acetazolamide administration was observed and mesured with this method in five patients with unilateral occlusive vascular pathology. These results suggest that this non-invasive method (without any blood sampling) permits the routine measurement of rCBF from HMPAO SPET tomograms of blood flow. Correspondence to: H. Matsuda     

Motor stimulation response by technetium-99m hexamethylpropylene amine oxime split-dose method and single photon emission tomography

We applied the technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) split-dose method in order to evaluate the feasibility of assessing cerebral blood flow (CBF) changes with single photon emission tomography (SPET) during a motor activation task. Eleven normal subjects were studied using the Tomomatic 564 (Medimatic, DK). Five subjects were studied twice at rest and 6 subjects at rest and during a motor task performance (finger opposition movements). A total of 28 mCi of ^99mTc-HMPAO was injected in 2 doses with a 1:3 ratio. The first scan was obtained after injection of 7 mCi at rest in all subjects. The second scan was obtained a few minutes later, after injection of the remaining dose (21 mCi), under similar resting conditions or during a motor task performance. The mean brain uptake was proportional to the amount of tracer injected and to the acquisition time for both the first scan (5263±1266 counts × mCi × min) and the second (5034.4±966 counts × mCi × min). The grey/white matter ratio was 1.67±0.019 and 1.67±0.097 for the two scans, respectively. A three-way analysis of variance (ANOVA) for repeated measure showed no significant effects of side, slice and region of interest (ROI) on the CBF in the 5 subjects studied twice at rest, and the mean regional CBF change was –0.2%±5%. In the 6 subjects studied at rest and during motor activation, the image subtraction analysis showed a significant CBF increase in the primary motor cortex contralateral to the stimulated side (15%±7%, n=6) and medially in the supplementary motor area (22%±12%, n=4). Our results indicate that the split-dose method allows the detection of a local CBF response to motor activation using ^99mTc-HMPAO in a single imaging session. Correspondence to: P. Pantano     

Parameters influencing SPET regional brain uptake of technetium-99m hexamethylpropylene amine oxime measured by calibrated point sources as an external standard

Using calibrated point sources as an external standard to convert single-photon emission tomography (SPET) brain counts into absolute values of regional brain uptake (rBU) of technetium-99m hexamethylpropylene amine oxime (HMPAO), the relative contribution of different parameters to interindividual variability of cerebellar rBU was examined in 33 healthy volunteers. Stepwise regression analysis identified body surface as the most important factor underlying interindividual variability (P<0.001), when compared with brain volume. In the normal volunteer population presented, age decrement of rBU corrected for body surface and brain volume equalled 60.5–0.20×age. Based on the data of eight normal volunteers, including four test-retest studies with heart rate (HR) differences greater than 5 units and four test-stress studies with doubling of heart rate after bicycle exercise, influence of heart rate may be expressed by the equation rBU=0.35 HR. Clinically, estimation of the relative influence of different factors allows normalization and extension of the applicability of the rBU quantification method used from longitudinal studies to group comparisons. Interestingly, results of the Daily Stress Inventory Scale and a subjective rating scale suggest the absence of a significant influence of minor stress on rBU. When using one vial per patient, chromatography may be omitted in clinical routine practice and lipophilicity may be estimated as 90% of the injected dose, if administered within 10 min after preparation. Finally, sensitivity of the quantification method was tested in eight volunteers using acetazolamide brain activation and showed a mean increase in cerebellar rBU of 30.2%, varying between 14.1% and 75.9%.     

Technetium-99m hexamethylpropylene amine oxime labelled leucocyte scintigraphy in ulcerative colitis and Crohn's disease

Technetium-99m hexamethylpropylene amine oxime labelled leucocyte scintigraphy (LS) was performed on 45 occasions in 30 patients with ulcerative colitis and on 53 occasions in 34 patients with Crohn's disease. Serial images were taken following re-injection of the labelled leucocytes. The segmental extent of the inflammation and the grade of the leucocyte uptake were calculated, and compared with the laboratory results and colonoscopy findings. The sensitivity and specificity of LS proved higher in ulcerative colitis (87% and 93%) than in Crohn's disease (53% and 89% in cases with large intestine involvement, and 82% and 100% in cases with small intestine involvement). The activity of the process determined by LS correlates with the ₂ globulin level (r=0.47), fibrinogen level (r=0.50), fS iron level (r=–0.57), sedimentation (r=0.44), leucocyte count (r=0.38), platelet count (r=0.34) and Best index (r=0.31) in ulcerative colitis, but not in Crohn's disease. Correspondence to: M. Papós     

Quantification of technetium-99m hexamethylpropylene amine oxime brain uptake in routine clinical practice using calibrated point sources as an external standard: phantom and human studies

Quantitative methods for calculation of regional cerebral blood flow with technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) have been proposed. These methods are very labour intensive and therefore are not useful in routine clinical practice. We describe a simple alternative method, using calibrated point sources as a scaling factor, whereby the tomographic slices are displayed as regional ^99mTc-HMPAO brain uptake per cm³ brain tissue in 10^–6 of the injected lipophilic dose. The method was validated on Jaszczak and Hoffman phantoms using a three-detector system with HR parallel and HR fan-beam collimators. Under the optimal conditions described in this paper, the measured to real activity ratio was 1.00 (SD = 0.06). The reproducibility of the cerebellar uptake in a group of ten normal volunteers and five patients was studied. Intra-individually a mean deviation of 12.6% was observed for the total group. For those persons with a heart rate difference of less than 5 units between the two studies, a mean deviation of 7.2% was obtained. Quantitative ^99mTc-HMPAO brain uptake images can be useful for longitudinal studies, especially for follow-up, activation and pharmacological studies. Correspondence to: A. Dobbeleir     

Application of technetium-99m hexamethylpropylene amine oxime single-photon emission tomography to neurologic prognosis in patients undergoing urgent carotid surgery

In this study we aimed to work out a quantitative prognostic index for preoperative assessment of brain technetium-99m hexamethylpropylene amine oxime (HMPAO) single-photon emission tomography (SPET) in patients referred for urgent carotid endarterectomy due to acute obstructive disease of the internal carotid artery (ICA) and neurological deficit. To this end we compared data from preoperative SPET studies with the postinterventional changes in neurological status in 20 patients (17 males, three females; mean age 53 years, SD 4 years) with acute ischaemic cerebral disorders induced by obstruction of the ICA. Carotid obstruction was diagnosed by ultrasound B-mode study. All patients underwent urgent carotid endarterectomy from the ICA. Patients were divided into two groups in accordance with the results of postoperative follow-up: group A comprised patients with significant (more than 3 points) postoperative improvement in neurological condition as quantified by the Canadian Neurological Scale (11 patients); group B consisted of patients with minimal improvement or deterioration (nine, three of whom died). All patients were studied preoperatively by^99mTc-HMPAO SPET. The volume of nonperfused tissue (VS, cm³) was quantified using the Mountz technique. Hypoperfused volume (V _hypoperf, cm³) in the affected hemisphere was calculated as the total volume of voxels with^99mTc-HMPAO uptake <90% of the contralateral symmetric voxels. Discriminant prognostic function was calculated by discriminant analysis as:PF = 0.072×VS + 29.46×(VS/V _hypoperf). Patients with preoperativePF values <8.20 demonstrated postoperative improvement in neurological status, while the group withPF>8.90 comprised patients who demonstrated minimal improvement or deterioration. PF values in the range 8.20–8.90 carried an indefinite prognosis. We conclude that the preoperative^99mTc-HMPAO SPET can be used for the selection of patients in whom improvement in neurological status may be expected after urgent surgical correction of acute extracranial obstruction of the ICA.     

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 (R_stimulation— R_deprivation)/R_deprivation 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.     

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.     

Diagnosis of brain death with technetium 99m hexamethylpropylene amine oxime

We report on the utility of technetium 99m hexamethylpropylene amine oxime (^99mTc-HMPAO) to diagnose brain death following cardiac surgery on a 49-year-old man with triple-vessel coronary artery disease. The imaging parameters and criteria to diagnose irreversible brain damage (brain death) with ^99m-TcHMPAO are outlined. Brain imaging with this tracer seems to be more reliable than classic radionuclide angiography and has a potential value to confirm the diagnosis of brain death at an early stage. In addition, it may be used to evaluate the perfusion pattern to other vital organs with potential for transplantation.Partially presented as a poster demonstration to the 19th Annual Meeting of the BNMS. Offprint requests to: D.C. Costa