Jan B. A. Habraken

Cerebral blood flow changes during script-driven imagery in police officers with posttraumatic stress disorder.

BACKGROUND Functional brain imaging studies in posttraumatic stress disorder (PTSD) have focused mostly on war or sexual abuse victims, many of whom also had comorbid disorders. The aim of this study was to examine the neuronal circuitry underlying responses to script-driven imagery in traumatized police officers with and without PTSD and with low comorbidity rates. METHODS In a case-matched control study, 30 traumatized police officers with and without PTSD underwent clinical assessment and (99m)technetium-hexa-methyl-propylene-amine-oxime single photon emission computed tomography scanning with neutral and trauma scripts. Statistical parametric mapping was applied to analyze changes in regional cerebral blood flow. RESULTS The main findings were significantly less activation in the medial frontal gyrus and more activation in the right cuneus in the PTSD group relative to the trauma-exposed control group in reaction to trauma versus neutral scripts. Within the PTSD group, subjects showed less activation in the superior temporal gyrus, left lentiform nucleus, left middle frontal gyrus, and left inferior frontal gyrus in reaction to trauma scripts. CONCLUSIONS We confirmed previous findings of dysfunction of the medial frontal gyrus in PTSD in a new population with low comorbidity rates. Other alterations were found in certain brain structures involved in emotional, memory, linguistic, visuospatial, and motor processing.

Effects of psychotherapy on regional cerebral blood flow during trauma imagery in patients with post-traumatic stress disorder: a randomized clinical trial

BACKGROUND Functional brain-imaging studies in post-traumatic stress disorder (PTSD) have suggested functional alterations in temporal and prefrontal cortical regions. Effects of psychotherapy on these brain regions have not yet been examined. METHOD Twenty civilian PTSD out-patients and 15 traumatized control subjects were assessed at baseline using psychometric ratings. Cerebral blood flow was measured using trauma script-driven imagery during 99mtechnetium hexamethyl-propylene-amine-oxime single-photon emission computed tomography scanning. All 20 out-patients were randomly assigned to treatment or wait-list conditions. Treatment was brief eclectic psychotherapy (BEP) in 16 weekly individual sessions. RESULTS At baseline, greater activation was found in the right insula and right superior/middle frontal gyrus in the PTSD group than in the control group. PTSD patients treated with BEP significantly improved on all PTSD symptom clusters compared to those on the waiting list. After effective psychotherapy, lower activation was measured in the right middle frontal gyrus, compared to the PTSD patients on the waiting list. Treatment effects on PTSD symptoms correlated positively with activation in the left superior temporal gyrus, and superior/middle frontal gyrus. CONCLUSIONS BEP induced clinical recovery in PTSD patients, and appeared to modulate the functioning of specific PTSD-related sites in the prefrontal cortical regions.

Dopamine transporter density in young patients with schizophrenia assessed with [(123)] FP-CIT SPECT

Disturbances in the dopamine (DA) system are thought to play a major role in schizophrenia. Amphetamine-induced release of endogenous DA is shown to be enhanced in schizophrenia, as is striatal [18F]FDOPA uptake in the striatum. It is not clear if the density of DA neurons is altered in schizophrenia. By studying the DA transporter with [123I]FP-CIT single photon emission computed tomography (SPECT), the density of nigrostriatal dopaminergic cells can be studied. Using [123I]FP-CIT SPECT, DA transporter density in the striatum was studied in 36 young patients with schizophrenia. Ten patients were antipsychotic (AP)-naive, 15 were treated with olanzapine, eight with risperidone and three were AP-free. A control group of 10 age-matched volunteers was included. Striatal [123I]FP-CIT binding was not significantly different between AP-naive patients (2.87), patients treated with olanzapine (2.76), patients treated with risperidone (2.76), AP-free patients (2.68) and controls (2.82) (F=0.07,p=0.98). Unexpectedly, striatal [123I]FP-CIT binding in females was significantly higher than in males (3.29 and 2.70, respectively; t=-2.56, p=0.014).Concluding, functional changes in the dopaminergic system in schizophrenia are not likely to be reflected in a change in DA transporter density. Moreover, DA transporter density does not seem to be altered by AP medication.

Variations in 123I-metaiodobenzylguanidine (MIBG) late heart mediastinal ratios in chronic heart failure: a need for standardisation and validation.

BackgroundThere is lack of validation and standardisation of acquisition parameters for myocardial 123I-metaiodobenzylguanidine (MIBG). This lack of standardisation hampers large scale implementation of 123I-MIBG parameters in the evaluation of patients with chronic heart failure (CHF).MethodsIn a retrospective multi-centre study 123I-MIBG planar scintigrams obtained on 290 CHF patients (82% male; 58% dilated cardiomyopathy; New York Heart Association [NYHA classification] > I) were reanalysed to determine the late heart-to-mediastinum ratio (H/M).ResultsThere was a large variation in acquisition parameters. Multivariate forward stepwise regression showed that a significant proportion (31%, p < 0.001) of the variation in late H/M could be explained by a model containing patient-related variables and acquisition parameters. Left ventricular ejection fraction (p < 0.001), type of collimation (p < 0.001), acquisition duration (p = 0.001), NYHA class (p = 0.028) and age (p = 0.034) were independent predictors of late H/M.ConclusionsAcquisitions parameters are independent contributors to the variation of semi-quantitative measurements of cardiac 123I-MIBG uptake. Improved standardisation of cardiac 123I-MIBG imaging parameters would contribute to increased clinical applicability for this procedure.

Pinhole SPECT imaging of dopamine transporters correlates with dopamine transporter immunohistochemical analysis in the MPTP mouse model of Parkinson's disease.

The in vivo analysis of dopaminergic degeneration in animal models of Parkinsons disease (PD), using pinhole single photon emission computed tomography (SPECT), ideally should afford a serial study design, enabling the analysis of the degenerative process as well as the potential neuroprotective and/or restorative properties of drugs over time in living animals. Previously, we demonstrated that striatal dopamine transporter (DAT) levels in rats could be analyzed reproducibly, using pinhole SPECT with the DAT probe [(123)I]N-omega-fluoropropyl-2beta-carbomethoxy-3beta-{4-iodophenyl}nortropane (FP-CIT). However, the capacity of this approach to accurately detect a range of striatal DAT levels in the most widely used animal model of PD, i.e., the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse, remains to be determined. For this purpose, various levels of DAT were induced by treating c57BL/6J mice for 1, 3, or 5 days with MPTP (25 mg/kg ip), respectively. [(123)I]FP-CIT SPECT scans were performed 5 days after the last MPTP injection. Mice were perfused 6 days after the last MPTP injection, and the SPECT data were compared to ex vivo striatal and nigral DAT levels as measured by immunohistochemistry within the same animals. The analysis of striatal DAT levels using SPECT and DAT immunohistochemistry yielded highly comparable results on the percentage of DAT reduction in each MPTP group. The in vivo data showed a decrease of specific striatal to non-specific binding ratios by 59%, 82%, and 76% in mice treated for 1, 3, and 5 days, respectively. Moreover, a strong, positive correlation was observed between the in vivo and ex vivo parameters. The present study provides the first evidence that [(123)I]FP-CIT pinhole SPECT allows the accurate detection of a range of striatal DAT (i.e., losses of approximately 60-80%) levels in mice. Since such large dopaminergic lesions could be detected, this SPECT method may at least be useful for analyzing neuroprotective treatment with a clear-cut positive (i.e., complete protection) or negative (i.e., not any protection) effect. Whether this method is also useful for analyzing more subtle effects of neuroprotective treatment (partial protection) remains to be established, by studying mice with small dopaminergic lesions.

Evaluation of [123I]β-CIT binding with SPECT in controls, early and late Parkinson's disease

The main neuropathological feature in Parkinsons disease (PD) is a severe degeneration of the dopaminergic neurons in the substantia nigra resulting in a loss of dopamine in the striatum. Recently, a new radioligand (beta-CIT) for single photon emission computed tomography (SPECT) became available for in vivo imaging of the dopamine transporter on nerve endings of dopaminergic neurons in the striatum. The present results demonstrate that [123I]-beta-CIT SPECT allows a discrimination between early and late PD patients. In our opinion, these preliminary data suggest that [123I]-beta-CIT SPECT should be used from now on in longitudinal studies (such as the DATATOP study) in which the effects of (putative) neuroprotective interventions in PD are monitored.

Imaging of striatal dopamine transporters in rat brain with single pinhole SPECT and co-aligned MRI is highly reproducible.

A recently developed pinhole high-resolution SPECT system was used to measure striatal to non-specific binding ratios in rats (n = 9), after injection of the dopamine transporter ligand (123)I-FP-CIT, and to assess its test/retest reproducibility. For co-alignment purposes, the rat brain was imaged on a 1.5 Tesla clinical MRI scanner using a specially developed surface coil. The SPECT images showed clear striatal uptake. On the MR images, cerebral and extra-cerebral structures could be easily delineated. The mean striatal to non-specific [(123)I]FP-CIT binding ratios of the test/retest studies were 1.7 +/- 0.2 and 1.6 +/- 0.2, respectively. The test/retest variability was approximately 9%. We conclude that the assessment of striatal [(123)I]FP-CIT binding ratios in rats is highly reproducible.

Contrast-noise-ratio (CNR) analysis and optimisation of breast-specific gamma imaging (BSGI) acquisition protocols

BackgroundBreast cancer is one of the most prevalent forms of cancer in women. Breast-specific gamma imaging (BSGI) is a diagnostic imaging method that uses sestamibi-labelled 99Tc and a dedicated gamma camera to localize malignant lesions in breast tissue. The aim of this study is to investigate if the current acquisition protocol for BSGI at our hospital is optimized for the detection of lesions in our patients.MethodsWe analyzed patient data and performed a phantom study with a Dilon 6800 gamma camera. The patient data were collected from a group of 13 patients (740 MBq 99mTc-sestamibi, four views per patient were dynamically acquired with a frame duration of 30 s per frame and a total acquisition time of 8 min per view). Reduced-time static images were created, and contrast-to-noise ratios of identified hotspots were determined for different acquisition times. For the phantom study, we used a contrast detail phantom to investigate the contrast and resolution properties, within the range of relevant clinical acquisition parameters. The phantom was filled with a concentration of 80 MBq in 500 ml of water, and we dynamically acquired frames for a total acquisition time of 60 min using a general purpose (GP) collimator. To compare the GP collimator with the high-resolution collimator, a second acquisition was made for both collimators with a total acquisition time of 16 min.ResultsThe initial analysis of BSGI scans of the 13 patients showed that a dose reduction by a factor of 3 would not have reduced the number of observable hotspots in each of the acquired views. However, a subsequent systematic analysis of our protocol with a contrast-detail phantom showed that dose reduction results in a lower observability of hotspots, whereas increased doses resulted in a higher observability.ConclusionWe believe that the results of our phantom study are relevant for clinical practice and that further dose reduction cannot be recommended for the BSGI exams at our hospital and that an increase of the administered activity should be considered.

What is the value of emission tomography studies in patients with a primary glioblastoma multiforme treated by 192Ir brachytherapy

SummaryBackground. We studied the use of 201Thallium SPECT and L-[1-11C]-tyrosine PET in patients with a primary glioblastoma multiforme treated with 192Ir brachytherapy after surgery and external beam radiation therapy. We hypothesised that the patients most likely to benefit from further surgery after deterioration would be those with radiation necrosis and would be recognised by a negative emission tomography scan.Methods. Twenty-one patients underwent 201Thallium SPECT performed before brachytherapy, and this was repeated in 19 patients when recurrence was suspected. Nine patients also underwent a PET scan at the same time. Nine patients underwent a second operation.Findings. SPECT and PET were highly concordant concerning the prediction of radionecrosis and/or tumour recurrence. Repeat surgery did not lead to a significant increase in survival. There was no significant association between the duration of survival and tumour-to-background ratio but the number studied was small. Both SPECT and PET showed highly active lesions, which were proved to be recurrent tumour by clinical and histological follow-up.Conclusion. Although PET and SPECT are both highly sensitive in detecting active tumour tissue, emission tomography was not clinically valuable in the investigation of patients with a primary glioblastoma treated with brachytherapy.

A method to measure the absorbed dose of the thyroid during I-131 therapy, using a collar detector system and a SPECT acquisition

Purpose: Due to variations in biological half‐life, accurate thyroid dosimetry for I‐131 therapy is not trivial in clinical practice. In recent publications, systems are described to measure the uptake of I‐131 in the thyroid repeatedly over time. In this work, we present a method to calculate patient specific pharmacokinetics and absorbed dose using such a collar detector system (CoTI) in combination with a SPECT acquisition and a two‐compartment model fit. Methods: For three patients receiving I‐131 therapy for benign thyroid conditions, the complete uptake profile is measured over a period of 15 to 25 days after administration. A SPECT measurement is performed to assess the functional volume of the thyroid and the amount of I‐131 in the thyroid. The uptake profile measured in counts‐per‐second is converted to absolute activity in MBq using the absolute quantification of the SPECT. A two‐compartment model is used as a fit to the uptake data of the thyroid and to estimate the activity in the blood‐pool. The estimated absorbed dose to the thyroid is then calculated from the integral of the activity. The assessed parameters from the method (6‐ and 24‐h uptake, thyroid volume and I‐131 uptake concentration) are compared with the values as determined in clinical practice. Furthermore, the convergence of the calculated absorbed dose as a function of measurement series duration is determined to assess the required measurement duration of the uptake profile. Results: The two‐compartment model fit shows a good agreement with the measured data points. Resulting dynamic uptake profiles of the three patients differ from each other. The uptake percentages differ from the pretherapy I‐123 uptake measurements that are used in usual clinical practice, which shows the potential added value of the proposed method. The duration of the required measurement series appears to be patient dependent and therefore needs to be determined for each patient individually. The proposed method allows for a basic investigation of the individual dynamic uptake profile of I‐131 in the thyroid and the calculation of the absorbed dose. Conclusions: The proposed measurement method is feasible and easily implementable given a system that can measure the uptake of I‐131 in the thyroid repeatedly over time. The observed differences in dynamic uptake profiles and the differences in the absorbed thyroid dose as calculated with our method and the parameters of the usual clinical care support the relevance of the proposed method. In future studies, this approach may possibly be used for outcome prediction and therapeutic activity optimization.