Aapo Ahonen

[123I]β-CIT SPECT demonstrates decreased brain dopamine and serotonin transporter levels in untreated parkinsonian patients

Striatal dopamine transporters (DATs) and serotonin transporters (SERTs) were evaluated in untreated patients with Parkinsons disease (PD) and controls using single‐photon emission computed tomography (SPECT) with 2β‐carboxymethoxy‐3β‐(4‐iodophenyl)tropane ([123I]β‐CIT). The striatal DAT specific to non‐displaceable uptake ratios of 29, and the SERT uptake measurements of 27, PD patients were compared with those of 21 and 16 controls, respectively. The results were correlated with Unified Parkinsons Disease Rating Scale (UPDRS) scores, the Hoehn & Yahr stage, age, duration of the disease, and the major PD signs. The specific DAT binding in the caudate, the putamen and the caudate/putamen ratio were measured. In all of the PD patients the striatal uptake values were bilaterally reduced, being 36.9% (P < 0.001) lower than those of the controls. In the hemiparkinsonian patients the reduction was greater on the side contralateral to the initial symptoms (33.3% vs. 27.8%) and the uptake ratios indicated a more pronounced deficit in the putamen (39.1%) than in the caudate (27.9%). The DAT uptake correlated with the UPDRS total score and activities of daily living (ADL) and motor subscores, the Hoehn & Yahr stage, and rigidity score. PD patients had significantly higher caudate to putamen ratios than the controls. In the PD patients the SERT values were lower in the thalamic and frontal regions. The SERT uptake ratio of the frontal area correlated with the UPDRS subscore I. [123I]β‐CIT SPECT provides a useful method for confirming the clinical diagnosis of PD with correlation to disease severity. Additionally, this technique allows the simultaneous measurement of SERT uptake and shows that PD patients, interestingly, seem to have decreased SERT availability in the thalamic and frontal areas. Mov. Disord. 16:124–130, 2001.

Complementary Roles of 18F-DOPA PET/CT and 18F-FDG PET/CT in Medullary Thyroid Cancer

Serum calcitonin and carcinoembryonic antigen (CEA) are markers of recurrent or persistent disease in medullary thyroid cancer (MTC). However, conventional imaging often fails to localize metastatic disease. Our aim was to compare fluorine-labeled dihydroxyphenylalanine (18F-DOPA) and 18F-FDG PET/CT with multidetector CT (MDCT) and MRI in recurrent or persistent MTC. Methods: Nineteen MTC patients with increased calcitonin or CEA on follow-up (mean ± SD, 93 ± 91 mo; range, 4–300 mo) after primary therapy were prospectively imaged with 4 techniques: 18F-DOPA PET/CT, 18F-FDG PET/CT, MDCT, and MRI. Images were analyzed for pathologic lesions, which were surgically removed when possible. The correlation between the detection rate for each method and the calcitonin and CEA concentrations and histopathologic findings was investigated. Results: On the basis of histology and follow-up, one or more imaging methods accurately localized metastatic disease in 12 (63%) of 19 patients. The corresponding figures for 18F-DOPA PET/CT, 18F-FDG PET/CT, MDCT, and MRI were 11 (58%) of 19, 10 (53%) of 19, 9 (47%) of 19, and 10 (59%) of 17, respectively. Calcitonin and CEA correlated with 18F-DOPA PET/CT (P = 0.0007 and P = 0.0263, respectively) and 18F-FDG PET/CT findings (both P < 0.0001). In patients with an unstable calcitonin doubling time (n = 8), 18F-DOPA and 18F-FDG PET/CT were equally sensitive. In contrast, for patients with an unstable CEA doubling time (n = 4), 18F-FDG PET/CT was more accurate. Conclusion: For most MTC patients with occult disease, 18F-DOPA PET/CT accurately detects metastases. In patients with an unstable calcitonin level, 18F-DOPA PET/CT and 18F-FDG PET/CT are complementary. For patients with an unstable CEA doubling time, 18F-FDG PET/CT may be more feasible. MRI is sensitive but has the highest rate of false-positive results.

Gamma scintigraphic evaluation of the fate of microcrystalline chitosan granules in human stomach.

In several reports of in vitro studies it has been suggested that the mucoadhesive chitosans could be of value in preparing gastro-retentive formulations. The aim of this study was to obtain direct in vivo evidence of whether microcrystalline chitosan (MCCh) formulations acted as gastro-retentive systems in humans. Neutron-activation-based gamma scintigraphy was used to study gastric residence times of MCCh granules in healthy male volunteers. Possible effects of neutron irradiation on the properties of the MCCh granules were studied in advance, in vitro. In vivo gamma scintigraphic evaluations were carried out with the subjects in a fasted state, using granules containing 95% (F1) or 40% (F2) of MCCh of molecular weight 150 kDa. Reference formulation (F3) was lactose granules. The reference granules passed rapidly from the stomach (mean t50% 0.5+/-0.3 h (n=5)). MCCh in granules prolonged gastric residence times of the formulations in only a few cases (in one volunteer in the F1 group (n=4) and in two volunteers in the F2 group (n=5)). Maximum individual t50% values were 2.1 h (F1) and 2.3 h (F2). It was concluded that the in vivo mucoadhesion of MCCh formulations is erratic, and that the formulations studied are not reliable gastro-retentive drug delivery systems.

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.

Comparison of Five Parathyroid Scintigraphic Protocols

Objectives. We compared five parathyroid scintigraphy protocols in patients with primary (pHPT) and secondary hyperparathyroidism (sHPT) and studied the interobserver agreement. The dual-tracer method (99mTc-sestamibi/123I) was used with three acquisition techniques (parallel-hole planar, pinhole planar, and SPECT/CT). The single-tracer method (99mTc-sestamibi) was used with two acquisition techniques (double-phase parallel-hole planar, and SPECT/CT). Thus five protocols were used, resulting in five sets of images. Materials and Methods. Image sets of 51 patients were retrospectively graded by four experienced nuclear medicine physicians. The final study group consisted of 24 patients (21 pHPT, 3 sHPT) who had been operated upon. Surgical and histopathologic findings were used as the standard of comparison. Results. Thirty abnormal parathyroid glands were found in 24 patients. The sensitivities of the dual-tracer method (76.7–80.0%) were similar (P = 1.0). The sensitivities of the single-tracer method (13.3–31.6%) were similar (P = 0.625). All differences in sensitivity between these two methods were statistically significant (P < 0.012). The interobserver agreement was good. Conclusion. This study indicates that any dual-tracer protocol with 99mTc-sestamibi and 123I is superior for enlarged parathyroid gland localization when compared with single-tracer protocols using 99mTc-sestamibi alone. The parathyroid scintigraphy was found to be independent of the reporter.

Scintigraphic verification of adherence of a chitosan formulation to the human oesophagus

It is well known that adherence of a drug product, e.g. a gelatine capsule, to the oesophagus can cause oesophageal injury, which can be severe if the medicinal agent has corrosive properties. In a recent study we investigated by means of gamma scintigraphy whether chitosan granules dispensed in gelatine capsules had gastro-retentive properties. In one of ten volunteers the formulation lodged in the oesophagus. This case is reported here. The capsule adhered initially to the distal oesophagus. The capsule shell had started to disintegrate within 5 min, with some radioactivity detectable in the stomach. However, about two thirds of the radioactivity remained detectable in the oesophageal region for 1.75 h. This could be explained on the basis that there had been adherence not only of the gelatine shell but also of chitosan granules to the oesophageal mucosa. In evaluating potential for causing oesophageal injury it is not enough to consider only the mucoadhesive properties of the outermost layer of a drug product, because the filler may also have such properties. When new excipient materials are introduced, evaluation of their mucoadhesive tendencies is important.

Brain serotonin transporter binding of [123I]ADAM: within-subject variation between summer and winter data.

The neurotransmitter serotonin (5‐HT) controls several physiological functions, and a disturbance of the 5‐HT system is implicated in many psychiatric conditions. Seasonal variation has been suggested in the 5‐HT system. We investigated within‐subject seasonal variation in brain serotonin transporter (SERT) binding with the SERT‐ligand [123I]ADAM and single photon emission computed tomography (SPECT) in 12 healthy individuals. No systematic variation was found in the midbrain or thalamus areas between scans done in summer and winter. Our results suggest that factors other than season are more important in causing within‐subject variation of brain SERT binding between summer and winter. (Author correspondence: anu.koskela@helsinki.fi)

Clinical audit: development of the criteria of good practices

Clinical audit is a systematic review of the procedures in order to improve the quality and the outcome of patient care, whereby the procedures are examined against agreed standards for good medical RADIOLOGICAL procedures. The criteria of good procedures (i.e. the good practice) are thus the cornerstones for development of clinical audits: these should be the basis of assessments regardless of the type of the audit--external, internal, comprehensive or partial. A lot of criteria for good practices are available through the recommendations and publications by international and national professional societies and other relevant organisations. For practical use in clinical audits, the criteria need to be compiled, sorted out and agreed on for the particular aims of an audit (comprehensive or partial, external or internal). The national professional and scientific societies can provide valuable contribution to this development. For examination--or treatment-specific criteria--preliminary consensus needs to be obtained with the help of clinical experts, while clinical audits can be useful as a benchmarking tool to improve the criteria.

Brain Single Photon Emission Computed Tomography at Term Age for Predicting Cerebral Palsy after Preterm Birth

In order to assess the predictive value of neonatal brain perfusion with single photon emission computed tomography (SPET) with regard to neuromotor outcome at a corrected age of 18 months, 34 infants with birth weight <1,500 g and gestation age <34 weeks underwent brain technetium-99m ethylcysteinate dimer (99Tcm-ECD) SPET at term age. The perfusion defects were estimated by visual interpretation. Consecutive semiquantitative assessment was made in 26 cases and reference values for the tracer were collected from images of 17 preterm infants with normal outcome after the follow-up period. Relative regional cortical (frontal, sensorimotor, parietal and occipital), cerebellar and thalamic perfusion levels were evaluated in middle sagittal slices and hemispheric asymmetries in transaxial slices. Perfusion defects predicted cerebral palsy (CP) (n = 11) with 82% sensitivity, 70% specificity and 74% accuracy, the corresponding figures for ultrasound (US) being 73, 83 and 79%, respectively. The sensitivity of SPET in predicting moderate or severe CP (n = 7) was 100% and the specificity 67%, the corresponding figures for US being 71% and 74%, respectively. Brain SPET seems to identify the most severe forms of CP in preterm infants very well at term age, but cannot identify all mild ones. In addition to a low specificity, the radiation exposure restricts usefulness of the method for clinical purposes.

Combining FDG-PET and 99mTc-SPECT to predict functional outcome after coronary artery bypass surgery.

AIMS Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are suggested to improve clinical decision-making in ischaemic cardiomyopathy. Here, we present a unique cohort of patients who underwent nuclear medicine studies and cardiac magnetic resonance imaging (MRI) both before and 1 year after coronary artery bypass (CABG) surgery to assess benefit from surgery. METHODS AND RESULTS Before CABG, we applied three quantitative techniques using (18)F-fluorodeoxyglucose-PET and (99m)technetium-tetrofosmin-SPECT with a software tool to measure defects with hypoperfused but viable and non-viable myocardium in 15 patients. One method used solely PET, two others combined PET and SPECT at different thresholds. As a reference, we used change in left-ventricular (LV) function and volume by MRI. Preoperatively, ischaemic but viable areas detected by the method with a 10% threshold combining PET-SPECT and the PET-only method correlated significantly with preoperative regional wall thickening (WT; P = 0.03 and P = 0.005, respectively). When compared with global functional outcome (change in LV ejection fraction) and LV remodelling (change in end-diastolic volume) 1 year postoperatively, no correlation appeared with preoperative PET- or PET-SPECT-derived viable or non-viable tissue. Neither was any correlation observable between local change in WT and local preoperative defect size evaluated by any of these three methods. CONCLUSION Preoperatively, PET and PET-SPECT with 10% threshold detected dysfunctional myocardium, but all analysis methods failed to predict 1-year functional outcome assessed by MRI. In patients with three-vessel disease and heart failure, SPECT perfusion and PET viability study results show substantial heterogeneity; this should be considered when selecting patients for revascularization.