Eveline Donnemiller

Brain perfusion scintigraphy with 99mTc-HMPAO or 99mTc-ECD and 123I-beta-CIT single-photon emission tomography in dementia of the Alzheimer-type and diffuse Lewy body disease.

Dementia of the Alzheimer-type (DAT) is characterized by progressive cognitive decline, variably combined with frontal lobe release signs, parkinsonian symptoms and myoclonus. The features of diffuse Lewy body disease (DLBD), the second most common cause of degenerative dementia, include progressive cognitive deterioration, often associated with levodopa-responsive parkinsonism, fluctuations of cognitive and motor functions, psychotic symptoms (visual and auditory hallucinations, depression), hypersensitivity to neuroleptics and orthostatic hypotension. A recent report suggests that positron emission tomography studies in patients with degenerative dementia may be useful in the differential diagnosis of DAT and DLBD. However, the diagnostic role of single-photon emission tomography (SPET) studies remains to be established. The aim of this study was therefore to evaluate regional cerebral perfusion [with either technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) or99mTc-ethyl cysteinate dimer (99mTc-ECD) SPET] and striatal dopamine transporter density [using iodine-123 2β-carboxymethoxy-3β-[4-iodophenyl]tropane (123I-β-CIT) SPET] in patients with DAT and DLBD. Six patients with probable DAT and seven patients with probable DLBD were studied. Blinded qualitative assessment by four independent raters of99mTc-HMPAO or99mTc-ECD SPET studies revealed bilateral temporal and/or parietal hypoperfusion in all DAT patients. There was additional frontal hypoperfusion in two patients and occipital hypoperfusion in one patient. In the DLBD group, regional cerebral perfusion had a different pattern. In addition to temporoparietal hypoperfusion there was occipital hypoperfusion resembling a horseshoe defect in six of seven patients. In the DAT group, the mean 3-h striatal/cerebellar ratio of123I-β-CIT binding was 2.5±0.4, with an increase to 5.5±1.1 18 h after tracer injection. In comparison, in the DLBD patients the mean 3-h striatal/cerebellar ratio of123I-β-CIT binding was significantly reduced to 1.7±0.3, with a modest increase to 2.1±0.4 18 h after tracer injection (P<0.05, Scheffe test, ANOVA). These results suggest that99mTc-HMPAO or99mTc-ECD and123I-β-CIT SPET may contribute to the differential diagnosis between DAT and DLBD, showing different perfusion patterns and more severe impairment of dopamine transporter function in DLBD than in DAT.

Impaired dopaminergic neurotransmission in patients with traumatic brain injury: a SPET study using 123I-β-CIT and 123I-IBZM

Abstract. Structural imaging suggests that traumatic brain injury (TBI) may be associated with disruption of neuronal networks, including the nigrostriatal dopaminergic pathway. However, to date deficits in pre- and/or postsynaptic dopaminergic neurotransmission have not been demonstrated in TBI using functional imaging. We therefore assessed dopaminergic function in ten TBI patients using [123I]2-β-carbomethoxy-3-β-(4-iodophenyl)tropane (β-CIT) and [123I]iodobenzamide (IBZM) single-photon emission tomography (SPET). Average Glasgow Coma Scale score (±SD) at the time of head trauma was 5.8±4.2. SPET was performed on average 141 days (SD ±92) after TBI. The SPET images were compared with structural images using cranial computerised tomography (CCT) and magnetic resonance imaging (MRI). SPET was performed with an ADAC Vertex dual-head camera. The activity ratios of striatal to cerebellar uptake were used as a semiquantitative parameter of striatal dopamine transporter (DAT) and D2 receptor (D2R) binding. Compared with age-matched controls, patients with TBI had significantly lower striatal/cerebellar β-CIT and IBZM binding ratios (P≤0.01). Overall, the DAT deficit was more marked than the D2R loss. CCT and MRI studies revealed varying cortical and subcortical lesions, with the frontal lobe being most frequently affected whereas the striatum appeared structurally normal in all but one patient. Our findings suggest that nigrostriatal dysfunction may be detected using SPET following TBI despite relative structural preservation of the striatum. Further investigations of possible clinical correlates and efficacy of dopaminergic therapy in patients with TBI seem justified.

Comparison of diffusion-weighted imaging and [123I]IBZM-SPECT for the differentiation of patients with the Parkinson variant of multiple system atrophy from those with Parkinson's disease

Both dopamine D2 receptor (D2R) binding single‐photon emission computed tomography (SPECT) with [123I]iodobenzamide (IBZM) and diffusion‐weighted imaging (DWI) have been shown to contribute to the differential diagnosis of patients with the Parkinson variant of multiple system atrophy (MSA‐P) and Parkinsons disease (PD). We aimed to compare these two routinely available functional imaging modalities in differentiating patients with MSA‐P from PD. For this purpose, results obtained by DWI and IBZM‐SPECT were intraindividually compared in a cross‐sectional study of 15 MSA‐P and 17 PD patients matched for age and disease duration. The activity ratios of striatal to frontal cortex uptake (S/FC ratio) were used as a semiquantitative measure of the relative density of basal ganglia dopamine receptors labeled by IBZM. Regional apparent diffusion coefficients (rADC) were determined in the striatum. MSA‐P patients had significantly lower S/FC ratios and significantly higher striatal rADCs than both PD patients and healthy volunteers. There were no significant differences in S/FC ratios and striatal rADC between PD patients and healthy volunteers. Sensitivity of IBZM‐SPECT versus DWI for the differentiation of MSA‐P from PD was 80% versus 93%, specificity 71% versus 100%, the predictive accuracy 75% versus 97%, the positive predictive value 71% versus 100%, and the negative predictive value 80% versus 94%. Striatal rADCs had a significant higher overall predictive accuracy than D2R binding with IBZM. In summary, our data suggest that DWI may be more accurate compared to IBZM‐SPECT in the differential diagnosis of MSA‐P versus PD.

Thallium-201 gated single-photon emission tomography for the assessment of left ventricular ejection fraction and regional wall motion abnormalities in comparison with two-dimensional echocardiography

Abstract. Simultaneous assessment of myocardial perfusion and function by gated single-photon emission tomography (GS) after a single tracer injection provides incremental information and is feasible with technetium-99m sestamibi. The present study validated the use of GS with thallium-201 for the assessment of left ventricular ejection fraction (LVEF) and regional wall motion by comparison with two-dimensional (2D) echocardiography (echo), which has not been done before. After injection of 111 MBq 201Tl at peak bicycle exercise (n=55) or pharmacological stress (n=17), GS was acquired 15 (post stress) and 120 min post injection (rest) on a double-head camera. An automatic algorithm (QGS) was used for processing. Echo (Acuson Sequoia C256) was performed immediately after rest GS. LVEFs assessed by GS and echo were correlated. The overall and segmental sensitivity and specificity of GS for the detection of regional wall motion abnormalities (WMAs) were calculated, echo serving as the gold standard. Perfusion abnormalities were scored. The success rate of the automatic algorithm was 100%, and visually assessed image quality was good to excellent in 88% of cases. Post-stress and rest LVEF as assessed by GS were highly correlated (r=0.91). Good correlations were obtained between post-stress LVEF (GS) and rest LVEF (echo) and between rest LVEF (GS) and rest LVEF (echo) (r=0.76 and 0.86 respectively). In patients with a reduced LVEF of less than 50% (n=23), these correlations were even better (r=0.84 and 0.89 respectively). Regional wall motion abnormalities (WMAs) were identified by GS with high sensitivity and specificity (88%–100% and 82%–98% respectively) and were directly related to the extent and severity of stress as well as of resting perfusion defects. It is concluded that GS with 201Tl is a feasible and reliable tool for the evaluation of patients with compromised left ventricular function in the context of coronary artery disease, and thus improves diagnosis and prognostic stratification. Regional WMAs were identified with high diagnostic accuracy and the method may prove helpful for the detection of myocardial viability.

Successful surgical treatment of insular epilepsy with nocturnal hypermotor seizures

Nocturnal hypermotor seizures (NHSs) suggest seizure onset in the frontal lobe. We present a patient with NHSs and insular seizure onset who underwent successful surgical treatment.

123I-β-CIT and 123I-IBZM-SPECT scanning in levodopa-naive Parkinson's disease

Striatal dopamine transporter function and dopamine D2 receptor status were evaluated in 15 patients with early untreated Parkinsons disease using single photon emission tomography (SPECT) with 123I‐Iodo‐2β‐carboxymethoxy‐3β‐(4‐idiophenyl)tropane (β‐CIT) and 123I‐Iodobenzamide (IBZM) as pre‐ and postsynaptic ligands. Symptoms were unilateral in five patients and bilateral but asymmetric in 10 patients. Patients with bilateral symptoms had significantly lower 18‐hour striatal/cerebellar β‐CIT binding ratios (3.59 ± 0.79) than hemiparkinsonian patients (5.76 ± 1.48, p < 0.05) reflecting more advanced disease in this subgroup. Patients with bilateral parkinsonism were also found to have a significant side‐to‐side difference in striatal β‐CIT binding with more marked reduction contralateral to the presenting limb (18‐hour striatal/cerebellar ratio: 4.13 ± 0.78 [ipsilateral] versus 3.59 ± 0.79 [contralateral], p < 0.05). Dopamine D2 receptor binding as measured by IBZM was significantly elevated contralateral to the affected side in hemiparkinsonian patients (striatal/cerebellar ratio: 2.42 ± 0.90 [contralateral] versus 2.19 ± 0.80 [ipsilateral], p < 0.05). This asymmetric upregulation was absent in the patients with bilateral parkinsonism (striatal/cerebellar ratio: 1.85 ± 0.43 [contralateral to more severely affected side] versus 1.83 ± 0.34 [ipsilateral], p > 0.05). Our data suggest that postsynaptic dopamine receptor upregulation contralateral to the presenting side occurs in untreated unilateral PD and disappears in untreated bilateral (asymmetric) PD despite a greater loss of dopamine transporter function. Combined β‐CIT and IBZM SPECT studies may be helpful to monitor the progression of nigrostriatal dysfunction in early PD.

Evaluation of Striatal Dopamine Transporter Function in Rats by in Vivo β-[123I]CIT Pinhole SPECT

Striatal dopamine transporter (DAT) function was evaluated in rats by in vivo SPECT-MRI coregistration using the radioligand 2-beta-carbomethoxy-3-beta-(4-[123I]iodophenyl)tropane (beta-[123I]CIT). The reconstructed transaxial resolution of 3.5 mm full width at half-maximum and the system sensitivity of 0.081 c/s/kBq using a 2.0-mm pinhole collimator aperture provided adequate spatial detail and sufficient sensitivity for imaging striatal beta-[123I]CIT uptake. SPECT images, coregistered onto a MRI template, showed high accuracy in the coronal and transverse planes (maximum mismatch of 1.3 mm). Following estimation of the in vivo binding equilibrium of beta-[123I]CIT in the healthy rat striatum, we evaluated the 6-hydroxydopamine-induced loss of striatal DAT function using beta-[123I]CIT SPECT and MRI coregistration and correlated these findings with dopaminergic cell counts in the substantia nigra pars compacta using TH immunohistochemistry. A subtotal unilateral DAT deficit was detected by beta-[123I]CIT SPECT in all animals which correlated significantly with the cell counting of the remaining dopaminergic neurons. beta-[123I]CIT pinhole SPECT provides a powerful and widely available tool for in vivo investigations of rat striatal DAT function. In contrast to classical autoradiography, the present method will be helpful in imaging dynamic changes of neurotransmission in the CNS by virtue of serial study designs. Depending on SPECT ligand availability, a wide range of other CNS receptors may be imaged as well using the presented in vivo technique.

Abnormalities of dopaminergic neurotransmission in SCA2: A combined 123I-βCIT and 123I-IBZM SPECT study

Extrapyramidal features may occur in spinocerebellar ataxias consistent with neuropathological evidence of nigrostriatal involvement. Recently, striatal dopaminergic neurotransmission was found to be abnormal in the uncommon parkinsonian presentation of spinocerebellar ataxia type 2 (SCA2). We have investigated, therefore, striatal dopamine transporter and D2 receptor function in a series of 9 patients with the more common ataxic presentation of SCA2 using single photon emission computed tomography and β‐CIT as well as IBZM. Age‐matched healthy subjects and patients with Parkinsons disease (PD) served as controls. All except 1 SCA2 patient exhibited slowness of limb movements without rigidity or rest tremor. In addition, cervical dystonia was present in 5 and dystonic head tremor in 2 SCA2 patients. Striatocerebellar (S/C) ratios of β‐CIT binding were significantly reduced in SCA2 patients compared to control subjects, and they were within the range of PD patients. S/C ratios of IBZM binding were significantly reduced in SCA2 patients compared to control subjects. We conclude that dopaminergic neurotransmission is impaired in the ataxic presentation of SCA2, with a prominent loss of striatal dopamine transporter function. Both slowness of limb movements as well as dystonia in the ataxic SCA2 phenotype may reflect dysfunction not only at cerebellar but also at basal ganglia level.

Mania caused by a diencephalic lesion

We describe the case of a young male patient, SN, who suffered a MR-documented ischaemic lesion of both dorsomedial thalami and presented with a transient maniform syndrome. SNs neuropsychological, structural and functional imaging findings are compared with similar reported cases and are discussed in the framework of fronto-subcortical circuits and their proposed behavioural disorders. SNs mania was characterized by restlessness, mood elevation, a tendency for pleasurable activities, inflated self-esteem and loss of disease awareness. Other symptoms were sexual disinhibition, tactlessness, abnormal discourse, and reduced need for food and sleep. His neuropsychological assessment revealed an anterograde amnesia, and an impairment of frontal-executive functions. A SPECT-study showed diaschisis-related areas of hypoperfusion in both prefrontal regions which were interpreted as equivalents of SNs frontal-dysexecutive syndrome. In addition, there was a perfusion deficit in the right orbitofrontal cortex, which was taken as the imaging correlate of SNs secondary mania and personality disorder. These findings suggest that SNs mania and his other symptoms result from the twofold disruption of fronto-subcortical connections, namely of the right orbitofrontal loop which is concerned with mood regulation and socially appropriate behaviour, and of the dorsolateral prefrontal loop which mediates executive cognitive functions.

Multimodality Cranial Image Fusion Using External Markers Applied via a Vacuum Mouthpiece and a Case Report

Purpose: To present a simple and precise method of combining functional information of cranial SPECT and PET images with CT and MRI, in any combination. Material and Methods: Imaging is performed with a hockey mask-like reference frame with image modality-specific markers in precisely defined positions. This frame is reproducibly connected to the VBH vacuum mouthpiece, granting objectively identical repositioning of the frame with respect to the cranium. Using these markers, the desired 3-D imaging modalities can then be manually or automatically registered. This information can be used for diagnosis, treatment planning, and evaluation of follow-up, while the same vacuum mouthpiece allows precisely reproducible stereotactic head fixation during radiotherapy. Results: 244 CT and MR data sets of 49 patients were registered to a root square mean error (RSME) of 0.9 mm (mean). 64 SPECT-CT fusions on 18 of these patients gave an RMSE of 1.4 mm, and 40 PET-CT data sets of eight patients were registered to 1.3 mm. An example of the method is given by means of a case report of a 52-year-old patient with bilateral optic nerve meningioma. Conclusion: This technique is a simple, objective and accurate registration tool to combine diagnosis, treatment planning, treatment, and follow-up, all via an individualized vacuum mouthpiece. Especially for low-resolution PET and even more so for some very diffuse SPECT data sets, activity can now be accurately correlated to anatomic structures.Ziel: Vorstellung einer einfachen und präzisen Methode zur Korrelation nuklearmedizinischer Bildgebung (SPECT und PET) des Schädelbereichs mit CT und/oder MRT. Material und Methodik: Die Bildgebung erfolgt mit einem externen helmartigen Referenzrahmen mit integrierten modalitätsspezifischen Markern an definierten Positionen. Die genaue Relation des Rahmens zum Schädel ist durch reproduzierbares Aufstecken auf das VBH-Vakuummundstück gewährleistet. Mittels dieser Marker können die jeweiligen Datensätze manuell oder (halb)automatisch registriert werden. Die so fusionierten Bilder können in der Diagnostik, Bestrahlungsplanung und Nachsorge eingesetzt werden; das Vakuummundstück dient gleichzeitig der präzisen Lagerung bei fraktionierter stereotaktischer Bestrahlung. Ergebnisse: 244 CT- und MRT-Datensätze von 49 Patienten wurden mit einem durchschnittlichen “root square mean error” (RSME) von 0,9 mm überlagert, während an 18 Patienten 64 CT-SPECT-Fusionen zu einem RSME von 1,4 und 40 CT-PET-Datensätze von acht Patienten zu 1,3 mm fusioniert wurden. An einer 52-jährigen Patientin mit bilateralem Optikusscheidenmeningiom wird die Methode beispielhaft demonstriert. Schlussfolgerung: Diese Methode ist ein einfaches, objektives und genaues Verfahren zur Registrierung multimodaler Datensätze. Insbesondere die Integration von Datensätzen mit niedriger Auflösung (PET und SPECT) erlaubt bedeutende Einblicke in klinische Vorgänge, die teilweise aus CT bzw. MRT nicht ersichtlich sind.