Kristian Liewendahl

DIAGNOSIS OF ACUTE HERPES SIMPLEX ENCEPHALITIS BY BRAIN PERFUSION SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY

Brain perfusion was studied in 14 patients with acute encephalitis by use of 123I-iodoamphetamine or 99mTc-hexamethylpropyleneamine oxime and single photon emission computed tomography (SPECT), the first examination being made 4-11 days after onset of encephalitis symptoms. All 6 patients with herpes simplex virus encephalitis (HSVE) had strongly increased accumulation of radiotracer in the affected temporal lobe; in the remaining 8 results were normal. At the time of the first SPECT conventional CT images were normal in all patients. The SPECT abnormality in HSVE gradually converted over 4-10 weeks from increased tracer accumulation to greatly subnormal accumulation. Brain perfusion SPECT may be helpful in the early diagnosis of HSVE.

99Tcm-HMPAO SPECT in suspected dementia

To evaluate the usefulness of 99Tcm-hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) in suspected dementia we studied 160 consecutively imaged elderly patients from our hospitals memory disorder clinic. The diagnosis was based on clinical data, laboratory tests, neuropsychological examination, computed tomography (CT) and EEG. The patients were divided into six diagnostic categories: Alzheimers disease (AD), multi-infarct dementia (MID), frontal lobe-type dementia (FTD), vascular encephalopathy not fulfilling the criteria of dementia, specific organic conditions, and psychiatric disorders. SPECT images were assessed without knowing the clinical diagnosis, and divided into AD pattern, FTD pattern, MID pattern, abnormal but unclassifiable, and normal. Twenty-three of 36 patients with clinical AD, 25/33 patients with clinical MID, and 2/5 patients with clinical TFD had compatible SPECT patterns. SPECT distinguished AD from MID in the majority (80%) of cases. In patients with depression or anxiety SPECT was abnormal in 16/21 cases, suggesting that SPECT may give early clues to the presence of an underlying organic disease in such elderly patients. Thus, SPECT with 99Tcm-HMPAO seems to be useful in the diagnosis of suspected dementia.

Indium-111 bleomycin complex for radiochemotherapy of head and neck cancer — dosimetric and biokinetic aspects

1 Department of Clinical Chemistry, University Central Hospital of Helsinki, Finland 2 Department of Otorhinolaryngology, University Central Hospital of Helsinki, Finland 3 Department of Onco[ogy, University Central Hospital of Helsinki, Finland 4 Department of Pathology, University of Helsinki, Finland 5 Department of Physics, University of Helsinki, Finland 6 Department of Radiation Physics University of Lund, Sweden

Accuracy of a registration procedure for brain SPET and MRI: Phantom and simulation studies

Phantom experiments and simulations were performed to evaluate the significance of different error sources in a clinical registration procedure for brain SPET and MRI based on external markers. The results from the phantom experiments were used to adjust the error model for simulations. In the phantom experiments, 13-14 external markers were attached to the surface of a three-dimensional brain phantom for computing registration. Three internal test markers were used to estimate the accuracy of registration. The phantom was imaged with two different SPET and MRI devices. The mean root-mean-squared (RMS) residual of the locations of the test markers after registration using different combinations of four external markers varied from 3.5 +/- 1.0 to 5.2 +/- 1.3 mm depending on the imaging equipment and parameters used. The accuracy improved with an increasing number of external markers, from 3.2 +/- 0.5 to 4.9 +/- 0.5 mm for 6 markers and from 3.1 +/- 0.1 to 4.7 +/- 0.1 mm for 13 markers. In simulations, the external markers had an error comparable to the corresponding error in the phantom experiments. The error in the test markers was varied independently of that of the external markers. When the locating error of the test markers was removed, about 2 mm of the residuals of the test markers were found to come from this source. When an error comparable to the resolution of the original images (7-10 mm for SPET, 2 mm for MRI) was included in the test markers, the largest mean RMS residual after registration was smaller than the resolution error (8.8 +/- 1.1 mm). This was due to the accuracy of localization of the external markers and the fact that the direction of the error was random for each marker. The size of the registration error of an image volume was site-dependent, being minimal near the centre of mass of the external markers. When comparing the error with the spatial resolution of SPET, it was concluded that the accuracy of registration is not the limiting factor in region-of-interest analysis of registered images, provided that the design and attachment of the marker system are appropriate.

Brain perfusion defect size in SPECT predicts outcome in cerebral infarction.

The results of previous reports on the usefulness of brain perfusion single photon emission computed tomography (SPECT) in predicting the outcome of patients with acute cerebral infarction are conflicting. We therefore studied brain perfusion in 64 patients with a single supratentorial infarction. Contradictory to previous results the perfusion defect volume estimated from transversal and coronal slices correlated significantly with both presenting clinical findings and outcome. Although the clinical status at admission also correlated well with outcome, there was a subgroup of patients in which the favourable outcome was predicted only by SPECT and not by physical or any other examination at admission.

Localization of melanoma with radiolabelled monoclonal antibody fragments and iodoamphetamine

In two melanoma patients, metastases accumulated both 99mTc-labelled monoclonal anti-tumor F(ab′)2 fragments and N-isopropyl-p-(123I)-iodoamphetamine. Small metastatic deposits were localized only by labelled antibody, for which a higher target-to-nontarget ratio was observed than for radioiodoamphetamine, indicating that immunoscintigraphy may be the more sensitive method. In these two patients positive immunohistochemical staining for the antibody used was observed, whereas in a third patient, with no concentration of labelled antibody, the staining result was negative showing the specificity of the immunoscintigraphy findings. It is possible that the accumulation of radio-iodoamphetamine is due to binding to melanin but this is not certain as tissue samples from one of the two patients with positive scintigrams did not contain stainable melanin.

Radioimmunodetection and Radioimmunotherapy of Malignant Melanoma: A Review

Radioimmunodetection utilizing monoclonal antibodies to various melanoma-associated surface antigens has been studied by several investigators during the past ten years. In the early trials, antibodies were labeled with 131I or 111In, but now 99mTc is almost exclusively used because of its more favorable energy for gamma camera imaging. Excellent specificity has been achieved in most studies, whereas sensitivity has been less good. In a recent European multicenter study on 493 patients sensitivity was 79% and specificity 96%. In this largest study on melanoma so far performed many previously unknown metastatic deposits were identified indicating that radioimmunodetection has a role in the management of metastatic disease. The clinical utility of immunoscintigraphy in localization of regional lymph node metastases has been documented in several investigations in recent years, indicating that this method can be used in the preoperative evaluation of patients. Radioimmunodetection has also been successfully used in the differential diagnosis of ocular lesions. However, conclusive evidence of improved patient outcome resulting from the earlier detection of melanoma lesions by immunoscintigraphy is still lacking. Anti-melanoma antibodies labeled with alpha- and beta-emitting isotopes are potential therapeutic agents, but so far there is little clinical experience with radioimmunotherapy of metastatic melanoma.

Transmission imaging for registration of ictal and interictal single-photon emission tomography, magnetic resonance imaging and electroencephalography.

Abstract.A method developed for registration of ictal and interictal single-photon emission tomography (SPET), magnetic resonance imaging (MRI) and electroencephalography (EEG) is described. For SPET studies, technetium-99m ethyl cysteinate dimer (ECD) was injected intravenously while the patient was monitored on video-EEG to document the ictal or interictal state. Imaging was performed using a triple-head gamma camera equipped with a transmission imaging device using a gadolinium-153 source. The images (128×128 pixels, voxel size 3.7×3.7×3.6 mm3) were reconstructed using an iterative algorithm and postfiltered with a Wiener filter. The gold-plated silver electrodes on the patient’s scalp were utilized as markers for registration of the ictal and interictal SPET images, as these metallic markers were clearly seen on the transmission images. Fitting of the marker sets was based on a non-iterative least squares method. The interictal SPET image was subtracted from the ictal image after scaling. The T1-weighted MPRAGE MR images with voxel size of 1.0×1.0×1.0 mm3 were obtained with a 1.5-T scanner. For registration of MR and subtraction SPET images, the external marker set of the ictal SPET study was fitted to the surface of the head segmented from MR images. The SPET registration was tested with a phantom experiment. Registration of ictal and interictal SPET in five patient studies resulted in a 2-mm RMS residual of the marker sets. The estimated RMS error of registration in the final result combining locations of the electrodes, subtraction SPET and MR images was 3–5 mm. In conclusion, transmission imaging can be utilized for an accurate and easily implemented registration procedure for ictal and interictal SPET, MRI and EEG.

Anti-melanoma antibodies bind preferentially to diploid metastases in immunoscintigraphy.

Immunoscintigraphy with 99Tcm-labelled anti-melanoma monoclonal antibody F(ab)2- fragments was performed in 23 patients with histologically verified metastatic melanoma. Immunoscintigraphy was positive in 14 patients and all known metastases were detected in eight patients, five of whom had only one lesion. Lesion localization and detectability were as follows: 12/13 (92%) cutaneous and subcutaneous, 11/14 (79%) lymph node, 5/7 (71%) bone, 3/6 (50%) lung and 1/5 (20%) abdominal metastases were visualized. Despite its high specificity - no false positive immunoscintigrams - the low sensitivity of this method in detecting deep metastases hampers its usability. The false negative results were not due to lack of antigen expression as positive immunostaining results were observed also in specimens from patients with negative immunoscintigrams. Flow cytometric analysis of the metastases revealed that in 7/8 (88%) patients with diploid tumours had positive immunoscintigrams but only 7/15 (47%) patients with aneuploid tumours. These results show that the diagnostic accuracy of melanoma immunoscintigraphy can be improved by selecting patients not only by testing for the antigen but also on the basis of DNA analysis of an accessible lesion.

Radioimmunodetection of malignant solid tumours

An increased clinical utility of radiolabelled monoclonal antibodies (MoAb), recognizing a variety of different antigens expressed preferentially in malignant tissue, for localizing primary, metastatic and recurrent cancer has been documented in many recent investigations. This review focuses on both basic and practical aspects of radioimmunodetection in oncology and is a status report on the performance and limitations of radiolabelled antibody procedures currently applied to the clinical detection of malignant solid tumours. At this time clinically validated radioimmunodetection methods are available for colorectal, ovarian, breast, lung, thyroid medullary, and head and neck carcinoma, and melanoma. Recent advances in humanization of MoAb significantly improve the prospects of effective antibody-guided radiotherapy in the near future.