Karl Reichmann

Prospective use of subtraction ictal SPECT coregistered to MRI (SISCOM) in presurgical evaluation of epilepsy

Purpose:  In patients with drug‐refractory focal epilepsy, nonlesional magnetic resonance imaging (MRI) or discordant data of presurgical standard investigations leads to failure generating a sufficient hypothesis for electrode implantation or epilepsy surgery. The seizure‐onset zone can be further investigated by subtraction ictal single‐photon emission computed tomography (SPECT) coregistered to MRI (SISCOM). This is an observational study of a large consecutive cohort of patients undergoing prospective SISCOM to generate hypothesis for electrode implantation or site of epilepsy surgery.

Regional cerebral blood flow single-photon emission tomography with 99mTc-HMPAO and the acetazolamide test in the evaluation of vascular and Alzheimer's dementia

Abstract. The diagnostic potential of technetium-99m hexamethylpropylene amine oxime (HMPAO) following systemic administration of the cerebral vasodilator acetazolamide (acetazolamide test) was evaluated by regional cerebral blood flow (rCBF) single-photon emission tomography (SPET) in patients with Alzheimer’s disease (AD) or vascular dementia (VD). An initial, high-resolution SPET study was performed with 99mTc-HMPAO, and after 2 days the patients were re-evaluated with 99mTc-HMPAO following systemic administration of acetazolamide. Reconstructed SPET slices were evaluated visually and semiquantitatively by a semi-automatic rCBF map method. When 99mTc-HMPAO alone was used, bilateral hypoperfusion was found in the temporal and/or parietal regions in 33% (6/18) of the VD patients and in 70% (23/33) of the AD patients. The corresponding data obtained by quantitative evaluation were 41% (7/17) and 71% (15/21), respectively. The vascular reserve capacity, as determined with the acetazolamide test, was preserved visually in 22% (4/18) and quantitatively in 29% (5/17) of the VD patients, but in 73% (24/33) and 76% (16/21) of the AD patients. The differences in the perfusion patterns between the VD and AD patients were statistically significant (P<0.01, Fischer’s exact test). Of the VD patients with hypoperfusion (bilateral temporal and/or parietal), 4/6 (67%, visual evaluation) and 4/7 (57%, quantitative evaluation) had a decreased vascular reserve capacity as determined with the acetazolamide test. In the AD group of patients the corresponding results were 3/23 (13%) and 4/15 (27%). It is concluded that the acetazolamide test is promising in rCBF SPET to differentiate VD from AD.

Single photon emission tomography imaging of myocardial oxidative metabolism with 15-(p-[123I]iodophenyl) pentadecanoic acid in patients with coronary artery disease and aorto-coronary bypass graft surgery

A total of 29 patients with coronary artery disease (CAD) were investigated with 15-(p-[123I] iodophenyl)pentadecanoic acid (123I-IPPA) and sequential single photon emission tomography (SPET). Of these, 19 were studied after aorto-coronary bypass graft surgery. Some 13 patients without evidence of CAD served as a control group. Two SPET studies (early and late) were carried out within 45 min after intravenous administration of 200 MBq 123I-IPPA at peak sub-maximal exercise. Semi-quantification of uptake (related to perfusion) and turnover (linked to metabolism) was obtained by segmental comparison of oblique slices. Taking coronary arteriography as the “gold standard”, 123I-IPPA scintigraphy had the following figures of merit for sensitivity and specificity in the diagnosis of CAD: for the left anterior descending artery territory 93% and 95%, for the left circumflex artery region 96% and 92%, and for the right coronary artery territory 77% and 92%, respectively. In all, 90% of the reperfused myocardial segments showed an improvement of uptake. Of these, 61% exhibited increased turnover after revascularization and 39% had pathologic turnover and thus a dissociation of improvement of perfusion and oxidative metabolism after surgery.

Does the pretherapeutic tumor SUV in 68Ga DOTATOC PET predict the absorbed dose of 177Lu octreotate

PURPOSE Selection of candidates for peptide receptor radionuclide therapy (PRRT) is increasingly based on receptor positron emission tomography (PET) imaging, including the common tracer 68Ga DOTATOC. However, no studies have yet compared standardized uptake values (SUVs) and absorbed doses in this field. MATERIALS AND METHODS We retrospectively analyzed a consecutive cohort of 21 patients with 61 evaluable tumor lesions undergoing both pretherapeutic 68Ga DOTATOC-PET/CT (Biograph Duo [Siemens Medical Solutions, Erlangen, Germany]; PET acquisition, 75.3 ± 15.4 minutes postinjection; 117.3 ± 33.9 MBq 68Ga DOTATOC) and PRRT with Lu octreotate (7.47 ± 1.39 GBq; intratherapeutic tumor dosimetry with serial whole-body scans; 1, 2, and 4 days postinjection) at our institution. SUVs were compared with the tumor-absorbed doses per injected activity (D/A0) of the subsequent first treatment cycle. RESULTS The correlation of SUV and D/A0 was r = 0.72 (SUVmean) and r = 0.71 (SUVmax), both P < 0.001. Pancreatic origin and hepatic localization were associated with higher D/A0, and chromogranin A level and Ki-67 index had no influence on SUV or D/A0. High-SUV lesions (SUVmean >15; SUVmax >25) resulted in high D/A0 (>10 Gy/GBq) in 66.7% to 70.8% and low D/A0 (<5 Gy/GBq) in only 8.3% to 12.5% on subsequent PRRT. The mentioned low D/A0 range, on the other hand, was achieved by all lesions with SUVmean <7 or SUVmax <9. CONCLUSIONS Somatostatin receptor PET imaging may predict tumor-absorbed doses. The ability to indicate insufficient target irradiation by a low SUV could aid in selection of appropriate candidates for PRRT. However, larger series are needed to confirm and validate these initial findings.

Pharmacological targeting of the constitutively activated MEK/MAPK-dependent signaling pathway in glioma cells inhibits cell proliferation and migration.

Activated mitogen-activated protein kinase MAPK cascade leading to ERK1/2 phosphorylation is expressed in the majority of glial neoplasms and negatively correlates with survival time of patients. Here we show that ERK1/2 kinases are constitutively activated in glioma cell lines and stem cell-enriched primary cultures of glioblastoma. Pharmacological targeting of the activated MEK/ERK1/2 module with the MEK inhibitor U0126 attenuates cell cycle progression (11 out of 11 cell lines), impairs single (7 out of 10) and collective cell migration (9 out of 11) and abolishes single cell emigration from monolayers (4 out of 9). Attacking the activated MEK/ERK1/2 module thus partially blocks the tumorigenic potential of glial cancer cells on different levels and strongly suggests the application of combination molecularly targeted therapies to interfere more efficiently with glial tumor development and progression.

The relevance of interictal rCBF brain SPECT in temporal lobe epilepsy: Diagnostical value and effects of spatial resolution

Interictal rCBF-SPECT is frequently being used as an adjunctive method for localization of an epileptogenic area during presurgical evaluation of patients suffering from medically refractory temporal lobe epilepsy. This study retrospectively evaluates interictal rCBF-SPECT using Tc-99m-HMPAO in comparison to the results of MRI. The final results of surface EEG and ECoG and the postsurgical clinical results as to seizure frequency were used as a ‘gold-standard’ for the evaluation of both imaging procedures.As spatial resolution is discussed to be the major reason for higher sensitivity of F-18-DG-PET compared to rCBF-SPECT, special attention has been paid to the spatial resolution of the different SPECT systems being used in this study. In 55 patients the complete data set could be obtained retrospectively, 36 of them being evaluated using SPECT systems with relatively low spatial resolution (Picker Dyna 2000, Elscint Helix) and 19 pt. being evaluated using moderateto highresolution SPECT systems (ADAC Genesys, DSI Ceraspect). Overall sensitivity of the interictal rCBF-SPECT was 75%, with 69% for low-resolution systems and 84% for high-resolution systems. Approximately at the same time when our institution installed the ADAC Genesys, the MRI equipment was changed from the 1.5 T Philips Gyroscan S15 to the 1.5 T Philips Gyroscan ACS II, the latter allowing superior imaging opportunities. Overall sensitivity of MRI was 60%, with 56%, for the Gyroscan S15 and 68% for the Gyroscan ACS II. The overall positive predictive value (PPV) was 87% for the interictal rCBF-SPECT and 87% for the MRI. Due to the lack of true negative studies in this population specificity was not calculated. False lateralization using rCBF-SPECT occurred in 5 pt. (9%), however in 3 pt. the area of hypoperfusion correlated with a detectable MRI pathology, yet EEG/ ECoG revealed the epileptogenic focus to be elsewhere. In conclusion, the interictal rCBF-SPECT revealed reasonable sensitivity and PPV in pt. suffering from focal temporal lobe epilepsy and modern SPECT systems showed significantly improved results. Since there is a variety of possible reasons for regional cortical hypoperfusion, the interictal SPECT could add significant information prior to the application of ECoG. This specially appeared to be useful in patients with a normal MRI scan. Furthermore, in patients presenting with a clear pathology on MRI and a corresponding EEG focus, ECoG could be avoided if the interictal rCBF-SPECT additionally showed localized and singular involvement of the affected temporal lobe. ECoG was mainly applied in those patients with relatively wide-spread hypoperfusion additionally involving frontal or parietal cortical areas.

Semiquantifying regional cerebral blood flow by 123I-amphetamine (IMP) SPECT in cerebrovascular disorders: correlations with CBF indices by 133Xe inhalation method.

To examine the capacity of detecting regional cerebral blood flow (rCBF) disturbances in stroke, measurements with 133Xe inhalation and 123I-amphetamine (IMP) SPECT were performed within 1–2 days in 19 patients. IMP SPECT images in transverse sections consisting of outer and inner areas were correlated with 32 regions of 133Xe rCBF. 133Xe rCBF was assessed by ISI, CBF15, and F1. Inter hemispheric ratio correlation showed outer IMP uptake correlated better with 133Xe CBF indices than the inner one. With higher ratios of 133Xe rCBF, IMP uptake ratios were variable, suggesting less usefulness of this parameter in evaluation of mild ischemia. Values of IMP in outer regional hypo and hyperemic areas correlated better with those of 133Xe rCBF than the inner ones. In regional ratios of hypo and hyperemic areas from hemispheric mean, outer IMP uptake correlated with 133Xe CBF indices, reflecting regional disturbances of fast clearing tissue perfusion. Regression lines between ratios in 133Xe CBF and IMP uptake were located below one to one correlation, and dissociated more for hyperemic regions. IMP SPECT correlated better with 133Xe rCBF for tissues with reduced perfusion but underestimated hyperemic regions as measured with the 133Xe method. The data suggest outer cerebral IMP uptake evaluated by SPECT could reflect flow disturbances in the brain cortex.

Comparison of [18F]FDG-PET andl-3[123I]-iodo-α-methyl tyrosine (I-123 IMT)-SPECT in primary lung cancer

Objective: The aim of this study was to evaluatel-3[123I]-iodo-α-methyl tyrosine (IMT)-SPECT and FDG-PET in pulmonary lesions suspected to be lung cancer.Methods: Whole body PET (measured transmission corrected emission scans) was performed 45 minutes after i.v. injection of 222–370 MBq (6–10 mCi)18F-FDG on a Siemens PET scanner (ECAT EXACT 47) including 5–6 bed positions.123I-IMT-SPECT (chest) was performed after injection of 370 MBq (10 mCi) with a dual head camera (Picker Prism 2000) and commercially available reconstruction algorithms. Ten patients (6 male and 4 female) with suspected lung cancer were investigated. The results were compared to histological findings after surgery or bronchoscopic biopsies and CT.Results:123I-IMT-SPECT and FDG-PET were able to detect all 9 cases of lung cancer (1–8 cm in diameter). One case was true negative. Both imaging methods were true positive with respect to mediastinal lymph node metastases in one patient. The tumor/background ratio was higher with PET (8.20vs. 2.84).Conclusion: Despite the limited number of patients it may be concluded that IMT-SPECT as well as FDG-PET are suited to correctly diagnose lung cancer. Nevertheless, FDG-PET, if available, seems to be better suited because of the higher tumor/background ratio and better resolution.

Interventional brain SPECT—A review

Brain SPECT with HMPAO or ECD has—due to its short accumulation period—a rather high time resolution of approx. 60 sec. Compared to isopropyl amphetamine (I-123) and FDG-PET, shortlasting interventions may be evaluated by SPECT. Usually, a two-step approach is used, injecting one third of the dose under baseline conditions and two thirds during intervention. The first study is then subtracted from the second study, resulting in a “difference” image which allows to calculate the effect of the intervention. These interventional procedures may include drug, mechanical, and mental intervention as well as ictal, blood pressure and receptor intervention. Moreover, the difference of pCO2 after hyperventilation or hypoventilation may also be used as a stimulus. The above mentioned procedures are described in detail.

Brain single-photon emission tomography using technetium-99m bicisate (ECD) in a case of complex partial seizure

The clinical application of technetium-99m bicisate (ethyl cysteinate dimer, ECD) for ictal and interictal studies of regional cerebral blood flow (rCBF) in a patient suffering from medically intractable simple and complex partial seizures is reported. The interictal study was performed 60 min p.i. and the ictal studies were performed at 60 min p.i. using an annular crystal single-photon emission tomography (SPET) system dedicated for high-resolution brain SPET imaging. Visual evaluation of the studies was carried out, as well as semiquantitative measurement of regional tracer uptake. Magnetic resonance imaging (MRI) scans revealed atrophy of almost the complete left frontal lobe and the ventral parts of the left temporal lobe, including in part the temporomesial structures. The left parietal and occipital structures and the right hemisphere were normal. The interictal study showed a large perfusion defect involving the whole left frontal lobe as well as the left temporal lobe with remaining small areas of normal cortical tracer uptake. The ictal studies detected circumscribed hyperperfusion within the left mesial temporal lobe (ventral part of the hippocampus). Additionally an increase in perfusion could be seen within the entire remaining left temporal lobe. Semiquantitative evaluation of tracer uptake comparing both studies detected markedly increased uptake within the focus compared to the remaining left temporal lobe. On this basis the newly available tracer for studies of rCBF, 99mTc-bicisate, seems to be of value for the detection of epileptogenic foci. Additionally, the value of ictal rCBF studies in the presurgical evaluation of those patients presenting severe morphological alterations on MRI is clearly underlined by this case.