L. Cinotti

“Luxury perfusion” with99mTc-HMPAO and123I-IMP SPECT imaging during the subacute phase of stroke

To compare the merits of123I-isopropyl-iodoam-phetamine (123I-IMP) and99mTc-HMPAO in showing abnormal brain uptake distribution during cerebral ischemia, we studied ten patients during the subacute phase of their stroke, a period where metabolism and blood flow are frequently uncoupled. SPECT imaging was performed using both radiopharmaceuticals in the 10 patients from 48 h to 4 weeks after onset of symptoms. Two patients out of the 10 had similar defects with123I-IMP and99mTc-HMPAO SPECT, the location of the defects corresponding to the area of infarction observed on CT. Six patients had normal99mTc-HMPAO SPECT and abnormal123I-IMP SPECT with defects in the area of infarction shown by CT. The remaining 2 patients had hyperactive abnormalities on99mTc-HMPAO in areas corresponding to defects on the123I-IMP images. Two of the patients with SPECT mismatches were studied again more than 1 month after onset. On reexamination,99mTc-HMPAO SPECT which was previously normal or hyperactive became hypoactive with a focal area of decreased activity corresponding to the defect on123I-IMP. Crossed cerebellar diaschisis was found in 7 patients with99mTc-HMPAO and was absent for both123I-IMP and99mTc-HMPAO in 3. We suggest that SPECT with99mTc-HMPAO could show transient hyperemia not demonstrated by123I-IMP whereas in some cases cerebral infarction would be more difficult to demonstrate with99mTc-HMPAO than with123I-IMP. SPECT with both tracers is recommended to follow the evolution of strokes in terms of regional cerebral blood flow and tissue metabolism.

High and Low Grade Oligodendrogliomas (ODG): Correlation of Amino-Acid and Glucose Uptakes Using PET and Histological Classifications

Classification and treatment strategy of Oligodendrogliomas (ODG) remain controversial. Imaging relies essentially on contrast enhancement using CT or MRI. The aim of our study was to use positron emission tomography (PET) using [18F]-flurodeoxyglucose (FDG) and [11C]-L-methyl-methionine (MET) to evaluate metabolic characteristics of (ODG). We studied 19 patients with proven ODG, comparing standardised uptake values (SUV) and maximal tumor/contralateral normal tissues ratios (T/N). Imaging findings were compared with WHO, Smith and Daumas—Duport classifications. Uptake of FDG was decreased only in 8 patients, independently of grading, while MET uptake was always increased. MET uptake was significantly higher for high grade tumors grouped according to Smith or Daumas—Duport classifications, while no significant difference in MET uptake was found when using WHO classification. A different correlation was found between FDG and MET uptakes in normal tissues and high grade tumors. A trend for improved progression free survival was found for tumors that lacked contrast enhancement on MRI or those showing low FDG or MET uptake.In conclusion, MET appeared more sensitive than FDG to detect proliferation in ODG. The preferential protein metabolism, already noticeable for low-grade tumor, correlated with glucose metabolism and helped to separate, in vivo, high and low grade tumors.

Effects of GABAA receptors activation on brain glucose metabolism in normal subjects and temporal lobe epilepsy (TLE) patients. A positron emission tomography (PET) study Part I: Brain glucose metabolism is increased after GABAA receptors activation

Though gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the human central nervous system, the metabolic response to GABA system activation remains imperfectly known. We studied in vivo with positron emission tomography (PET) the variations of glucose metabolism in the human brain after stimulation of the GABAA receptors by systemic administration of the specific GABAA agonist, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP). These investigations were performed in three normal volunteers and as part of presurgical evaluation for temporal lobe epilepsy in six patients. While clinical and electroencephalographic (EEG) monitoring showed a sedative effect and sleepiness after THIP administration, glucose metabolism was paradoxically increased in grey matter structures, which are known to have a high density of GABAA receptors. These findings suggest that the pharmacological activation of GABA pathways, although inhibitory and producing a decrease of vigilance, increases the energetic demand at least during a phase of GABA agonist action, probably at the synaptic or at the glial cell level.

Effects of GABAA receptors activation on brain glucose metabolism in normal subjects and temporal lobe epilepsy (TLE) patients. A positron emission tomography (PET) study Part II: The focal hypometabolism is reactive to GABAA agonist administration in TLE

Positron emission tomography (PET) using [18F]fluorodeoxyglucose (FDG) was used to study the metabolic response of focal hypometabolism to the administration of a specific GABAA agonist (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), THIP, in six temporal lobe epilepsy (TLE) patients. After THIP injection, the increase of glucose metabolism in the hypometabolic focus was larger than the mean increase reported in the whole brain (Part I; Epilepsy Res., 19 (1994) 45-54). Within the hypometabolic focus, this increase was significantly higher in regions with the lowest basal metabolic level. This metabolic response in the hypometabolic focus, observed in the absence of any epileptic discharge during FDG accumulation and PET data acquisition, suggests that GABAA receptors are up-regulated or, at least, preserved in TLE.

Technetium-99m DTPA aerosol and gallium scanning in acquired immune deficiency syndrome

In 11 non-smoking AIDS patients suspected of pneumocystis carinii pneumonia (PCP), the results of Tc-99m DTPA aerosol clearances, gallium scans, and arterial blood gases were compared with those of bronchoalveolar lavage (BAL). Nine patients had PCP. All had increased clearances five times higher than the normal (5.6 ± 2.3% min-1 vs 1.1 ± 0.34% min-1, N=10,P< 0.001), suggesting an increased alveolar permeability. Gallium scans were abnormal in six patients but normal or slightly abnormal in the three others. Four of these nine patients had normal chest x-rays. In two of these the gallium scan was abnormal, but in the two others, only the increased Tc-99m DTPA clearances showed evidence of lung disease. Two patients had normal BAL, with normal clearances and gallium scans. Four out of the nine patients with PCP were studied after treatment. Three recovered and had normal clearance and gallium scans. One still had PCP with increased clearance but normal gallium scan. Gallium scanning and Tc-99m DTPA clearance are useful for detecting lung disease in AIDS patients with suspected PCP and for prompting BAL when chest x-rays and PaO2levels are normal.Due to its high sensitivity, a normal Tc-99m DTPA clearance could avoid BAL.

Factor analysis of medical image sequences improves evaluation of first-pass MR imaging acquisitions for myocardial perfusion.

RATIONALE AND OBJECTIVESnFactor analysis of medical image sequences (FAMIS) applied to gadolinium chelate-enhanced subsecond magnetic resonance (MR) imaging was evaluated as a postprocessing method for assessing myocardial perfusion in coronary artery disease (CAD).nnnMATERIALS AND METHODSnTo assess the accuracy of motion correction, five normal volunteers underwent MR imaging at rest. Thirteen patients with well-documented CAD and no myocardial infarction underwent MR imaging at rest and after dipyridamole administration. After motion correction, a single myocardial tissue factor (FAMISt) image was obtained with FAMIS for each raw MR imaging series acquisition. To evaluate how FAMIS could improve the analysis of these acquisitions, five readers visually assessed myocardial perfusion with FAMISt and raw MR images, and a multicase, multireader receiver operating characteristic analysis was performed.nnnRESULTSnFAMISt images significantly improved detection of the perfusion defects when compared with raw MR images (P = .002). Areas under the receiver operating characteristic curves ranged from 0.84 to 0.93 with FAMISt images and from 0.48 to 0.85 with raw MR images.nnnCONCLUSIONnFAMIS applied to first-pass MR imaging series provided myocardial perfusion images that improve the objective assessment of myocardial perfusion in patients with CAD.

Extraction of functional volumes from medical dynamic volumetric data sets

A method based on factor analysis is presented to process dynamic volumetric (t + 3D) data sets acquired for flow, excretion, or metabolic studies. It estimates a reduced number of underlying physiological kinetics and their associated spatial distributions, corresponding to functional volumes, using dedicated algorithms. The global (t + 3D) approach is shown to be superior to the conventional one, which repeats estimations on each (t + 2D) data set, obtained for each slice or projection of the volume.

Lung scintigraphy clustering by texture analysis.

The efficiency of texture analysis parameters, describing the organization of grey level variations of an image, was studied for lung scintigraphic data classification. Twenty one patients received a99mTc-MAA perfusion scan and81mKr and and127 Xe ventilation scans. Scans were scaled to 64 grey levels and 100 k events for inter subject comparison. The texture index was the average of the absolute difference between a pixel and its neighbors. Energy, entropy, correlation, local homogeneity and inertia were computed using co-occurence matrices. A principal component analysis was carried out on each parameter for each type of scan and the first principal components were selected as clustering indices. Validation was achieved by simulating 2 series of 20 increasingly heterogeneous perfusion and ventilation scans. For most of the texture parameters, one principal component could summarize the patients data since it corresponded to the relative variances of 67%-88% for perfusion scans, 53%–99% for81mKr scans and 38%–97% for127Xe scans. The simulated series demonstrated a linear relationship between the heterogeneity and the first principal component for texture index, energy, entropy and inertia. This was not the case for correlation and local homogeneity. We conclude that heterogeneity of lung scans may be quantified by texture analysis. The texture index is the easiest to compute and provides the most efficient results for clinical purpose.

Factor analysis of 81mKr lung ventilation studies.

Factor analysis of dynamic structures (FADS) summarizes data depending on time and space in a few elementary components. Each of them associates a time-activity curve (factor) and the spatial distribution of the corresponding events. The aim was to evaluate the patterns, the number of components, and their possible link to physiology when FADS was applied to scintigraphic images representing a composite of a 81mKr ventilation cycle. In a study of 26 patients (10 normal, 16 pathologic), components were found that represent: (1) a rapid and steeply changing ventilation factor, corresponding mainly to bases in normal subjects and whole lung fields in patients, (2) a slower expiration and shorter inspiration ventilation factor distributed throughout both lung fields in all patients, (3) a constant activity curve, with an inspiratory activity peak distributed over both lung fields and the large airways, and (4) a factor including a phase shift with respect to the first; this was found significantly more often in patients with pathology.

Evaluation of factor analysis accuracy for myocardial perfusion in PET studies

Factor Analysis of Medical Image Sequences (FAMIS) estimates kinetics (factors) and corresponding spatial regions (factor images) from dynamic studies, taking into account statistical noise and spillover effects. Factor images obtained from /sup 15/O-water clinical cardiac PET studies are less noisy than conventional subtraction images, and factors match physiologic kinetics. Here, the authors studied FAMIS accuracy and precision depending on the application context. FAMIS was evaluated through kinetics parameters quantification. Numerical simulations and phantom experiments were carried out using a typical left ventricular pattern. This object was simulated in 2D with 3 noise levels and 2 kinds of kinetics: mono-exponentials which correspond to natural tracer decay, and tissue perfusion kinetics obtained with a realistic vascular input function. Mono-exponentials association was adapted to phantom experiments while perfusion kinetics represented clinical cardiac studies. In both phantom experiments and simulations, the inner chamber was filled with /sup 15/O-water and the myocardial space with Carbon-11. The different noise levels which were studied corresponded to ideal, normal and low quality scans. Using the factors estimated by FAMIS, decay constants and an index of flow (k1) were estimated by fitting or modelling. Relative bias to the true value and standard deviation were then estimated, and spatial correlation between factor images and original spatial pattern was computed. Factor images spatial correlation was very good, despite of large overlapping pattern. Oxygen-15 decay constant was assessed from factor with a small relative bias, for all noise levels and trixel sizes. However, Carbon-11 extraction was very sensitive to both noise and spillover in phantom and simulations. A reasonable bias was only achieved by including a spillover term which accounted for an overcorrection. On the contrary, factors associated to perfusion were well extracted and k1 parameter was recovered with a low relative bias (r.b.<6%), except for the higher noise level. It was already shown that FAMIS performances depend on the overlap of the spatial structures. This study demonstrates that factor analysis without a priori information performances depend on kinetics shape. Moreover, in the context of cardiac /sup 15/O-water perfusion studies, FAMIS should provide accurate quantification.