Päivi Nikkinen

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.

Autologous bone marrow mononuclear cell transplantation in ischemic heart failure: A prospective, controlled, randomized, double-blind study of cell transplantation combined with coronary bypass

BACKGROUND Bone marrow mononuclear cell (BMMC) transplantation for heart failure has shown inconsistent therapeutic efficacy. METHODS We enrolled 104 ischemic heart failure patients scheduled for coronary artery bypass surgery (CABG). After 4- to 12-week pharmacotherapy optimization, 39 patients with left ventricular ejection fraction (LVEF) of ≤45% received injections of BMMC or vehicle intra-operatively into the myocardial infarction border area in a randomized, double-blind manner. RESULTS The median number of cells injected was 8.4 × 10(8) (interquartile range [IQR]: 5.2 × 10(8) to 13.5 × 10(8)). We measured LV function and myocardial scar size by magnetic resonance imaging (MRI), and viability by positron emission tomography (PET) and single-photon emission computed tomography (SPECT), pre-operatively and after 1-year follow-up. LVEF, the pre-defined primary end-point measure, improved by a median of 5.6% in the control group (IQR 0.2 to 10.1) and by 4.8% in the BMMC group (IQR -0.5 to 8.2) (p = 0.59). Wall thickening in injected segments rose by a median of 4.5% among controls (IQR -18.1 to 23.9) and by 5.5% in the BMMC group (IQR -6.6 to 26.5) (p = 0.68). Changes in viability by PET and SPECT did not differ between groups. Myocardial scar size by MRI in injected segments rose by a median of 5.1% among controls (IQR -3.3 to 10.8), but fell by 13.1% in the BMMC group (IQR -21.4 to -6.5) (p = 0.0002). CONCLUSIONS BMMC therapy combined with CABG failed to improve LV systolic function, or viability, despite reducing myocardial scar size.

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.

Registration and display of brain SPECT and MRI using external markers

Accurate anatomical localisation of abnormalities observed in brain perfusion single-photon emission computed tomography (SPECT) is difficult, but can be improved by correlating data from SPECT and other tomographic imaging modalities. For this purpose we have developed software to register, analyse and display99mTc-hexamethylpropyleneamine oxime SPECT and 1.0 T MRI of the brain. For registration of SPECT and MRI data external skin markers containing99mTc (220 kBq) in 50 μl of coconut butter were used. The software is coded in the C programming language, and the X Window system and the OSF/Motif standards are used for graphics and definition of the user interface. The registration algorithm follows a noniterative least-squares method using singular value decomposition of a 3×3 covariance matrix. After registration, the image slices of both data sets are shown at identical tomographic levels. The registration error in phantom studies was on average 4 mm. In the two-dimensional display mode the orthogonal cross-sections of the data sets are displayed side by side. In the three-dimensional mode MRI data are displayed as a surface-shaded 3 D reconstruction and SPECT data as cut planes. The usefulness of this method is demonstrated in patients with cerebral infarcts, brain tumour, herpes simplex encephalitis and epilepsy.

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.

Abdominal SPECT/MRI fusion applied to the study of splenic and hepatic uptake of radiolabeled thrombocytes and colloids

The importance of applying MRI (CT)/SPECT fusion in the abdominal and thoracic areas has been recognized in recent studies aiming at radionuclide therapy of cancer. According to our earlier results spleen and liver volume determination with different segmentation methods is inaccurate with SPECT alone. We therefore applied a SPECT/MRI registration procedure to the estimation of spleen and liver volumes and spleen/liver activity ratios in three male volunteers administered111In-labeled thrombocytes and99mTc-labeled colloids. The objectives of the study were to investigate if the uptake of thrombocytes in the spleen and liver can be measured more accurately when the anatomical borders of these organs are transferred from MRI to SPECT, and to test a SPECT/MRI registration method for improving three-dimensional dosimetry for radiotherapy treatment planning. A good correlation was found between spleen/liver activity ratios calculated from volumetric average activity per pixel values and from total volumetric counts derived from registered data but not from projection data. The average registration residual with this SPECT/MRI fusion method is approximately 1–2 cm in the abdominal area. Combining anatomical images with SPECT is therefore important for improving quantitative SPECT also in the abdomen.

Anti-alpha-fetoprotein imaging is useful for staging hepatoblastoma.

Background. Liver transplantation (Tx) has become an alternative treatment of malignant childhood liver tumors, and the importance of careful pretransplantation evaluation has been emphasized. Anti-alpha-fetoprotein (AFP) imaging has been suggested for evaluation of adult patients with AFP-positive tumors. Methods. Antibody imaging utilizing Tc-99 m-labeled monoclonal anti-AFP Fab′ fragments was used to demonstrate pathologic uptake in hepatoblastoma (HB). Results. Radical operation or liver Tx was not possible after four cycles of chemotherapy in a child with HB because of a single extrahepatic metastasis. Chemotherapy was continued, and reevaluation with anti-AFP imaging demonstrated a pathologic uptake only in the liver. Subsequently, a right liver lobe resection was performed. Along with a new rise in serum AFP, repeated anti-AFP imaging revealed active liver tumor but no metastases. A liver Tx was performed, and the child is well with a normal serum AFP level 18 months after the operation. Conclusion. This is the first case of pediatric HB in which anti-AFP imaging has been successfully used for patient management.

Personal radiation doses in PET/CT facility: measurements vs. calculations.

The estimation of shielding requirement of a new positron emission tomography (PET) facility is essential. Because of penetrating annihilation photons, not only radiation safety in the vicinity of patients should be considered, but also rooms adjacent to uptake and imaging rooms should be taken into account. Before installing a PET/CT camera to nuclear medicine facilities of Helsinki University Central Hospital (HUCH), a typical PET imaging day was simulated using phantoms. Phantoms were filled with 300 +/- 36 MBq of (18)F isotope and dose rates were measured at 12 central locations in the laboratory. In addition to measurements, dose rates were also calculated using guidelines of AAPM Task Group 108. The relationship between the measured and calculated dose rates was found to be good and statistically significant, using Pearsons correlation test. The evaluated monthly doses were compared with personal dosemeter readings. AAPMs report gives practical tools for evaluation of radiation shielding. Calculations can be carried out successfully for existing hospital complexes too. However, calculations should be carried out carefully, because especially doors, windows and partitions can easily cause underestimation of shielding requirements as shown in this work.

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.