Diagnostic approach with Z-score mapping to reduce artifacts caused by cerebral atrophy in regional CBF assessment of mild cognitive impairment (MCI) and Alzheimer's disease by [99mTc]-ECD and SPECT.

PURPOSE: The aim of this study was to develop a novel approach that enhanced diagnostic accuracy in the diagnosis of mild cognitive impairment (MCI) and early Alzheimer's disease (AD) using cerebral perfusion SPECT by minimizing artifacts caused by cerebral atrophy. MATERIALS AND METHODS: [99mTc]-ECD and SPECT studies were performed on 15 cognitively normal patients, 40 patients with MCI, and 16 patients with AD. SPECT images were compared using SPM. The atrophy correction method was incorporated to reduce artifacts through the MRI masking procedure. Regional Z-score, percent extent, and atrophy correction rate were obtained and compared. The Z-score mapping program was structured as a single package that ran semi-automatically. RESULTS: The method significantly reduced regional Z-score in most regions, leading to improved estimates. The mean atrophy correction rate ranged from 10.4 to 12.0%. In MCI and AD, the convexities of the frontal and parietal lobes and the posterior medial cerebrum were particularly sensitive to cerebral atrophy, and the Z-scores were overestimated, whereas the posterior cingulate cortex and the cerebellum were less sensitive. The diagnostic accuracy for MCI increased from 67 to 69% and for AD from 78 to 82%. CONCLUSION: The proposed approach provided more precise Z-scores with less over- or underestimation, artifacts, and improved diagnostic accuracy, being recommended for clinical studies.

Monitoring urinary mercapturic acids as biomarkers of human dietary exposure to acrylamide in combination with acrylamide uptake assessment based on duplicate diets.

The present human intervention study investigated the relation between the intake of acrylamide (AA) in diets with minimized, low, and high AA contents and the levels of urinary exposure biomarkers. As biomarkers, the mercapturic acids, N-acetyl-S-(carbamoylethyl)-L-cysteine (AAMA), and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) were monitored. The study was performed with 14 healthy male volunteers over a period of 9 days, under controlled conditions excluding any inadvertent AA exposure. Dietary exposure to AA was measured by determining AA contents in duplicates of all meals consumed by the volunteers. The study design included an initial washout period of 3 days on AA-minimized diet, resulting in dietary AA exposure not exceeding 41 ng/kg bw/d. Identical washout periods of 2 days each followed the AA exposure days (day 4, low exposure, and day 7, high exposure). At the respective AA intake days, volunteers ingested 0.6-0.8 (low exposure) or 1.3-1.8 (high exposure) µg AA/kg bw/d with their food. Both low and high AA intakes resulted in an AAMA output within 72 h corresponding to 58 % of the respective AA intake. At the end of the initial 3-day washout period, an AAMA baseline level of 93 ± 31 nmol/d was recorded, suggestive for an assumed net AA baseline exposure level of 0.2-0.3 µg AA/kg bw/d.

Scintigraphic assessment of renal function in steel plant workers occupationally exposed to lead.

OBJECTIVES: Occupational exposure to lead may produce kidney damage, but existing data on the dose range associated with nephrotoxicity are inconclusive. We here assessed renal function under conditions of low to moderate lead exposure using renal scintigraphy. METHODS: Fifty-three male foundrymen (exposed group) and fourty male office workers (control group) from a steel plant were included in the study. Glomerular and tubular renal function were assessed by means of (99m)Tc-DTPA and (99m)Tc-EC clearance, respectively. Urinary markers of glomerular dysfunction (albumin) and tubular damage (α1-microglobulin (α1M), ß2-microglobulin (ß2M), retinol-binding protein (RBP), N-acetyl-ß-glucosaminidase (NAG) activity) were determined using latex beads tests or colorimetry. The lead concentration in blood was measured with atomic absorption spectrometry. RESULTS: The blood lead concentrations were 145.8 (121.3-175.3) and 39.3 (35.1-44.1) µg/l (geometric mean, 95(th) CI, p<0.001) in the exposed and control groups, respectively. Subjects exposed to lead presented with increased (99m)Tc-DTPA clearance (158.3 (148.4-168.8) vs. 135.9 (127.9-144.4) ml/min; p<0.01) and urinary albumin excretion (7.61 (6.28-9.22) vs. 4.78 (4.05-5.65) mg/g creatinine; p<0.001). (99m)Tc-EC clearance and excretion of α1M, ß2M, RBP and NAG were not significantly different between the groups. Significant correlations between (99m)Tc-DTPA clearance and blood lead concentrations (r=0.45; p<0.01) and between urinary albumin excretion and blood lead concentrations (r=0.71; p<0.001) were noted. CONCLUSIONS: Use of renal scintigraphy in present study revealed measurable alterations of renal function under the conditions of low-level lead exposure and suggest that increased glomerular filtration may be an early indicator of kidney damage in subjects occupationally exposed to lead.

Preliminary assessment of interand intraobserver reproducibility, and normative values of renal mean transit time (MTT) and parenchymal transit time (PTT) for 99mTc-etylenodicysteine.

BACKGROUND: The clinical significance of MTT and PTT, determined by deconvolution of renographic curves, is arguable. Their usefulness in diagnosis of obstructive uro- and nephropathy, renovascular hypertension and monitoring of transplanted kidneys is pointed out, but susceptibility of deconvolution methods to errors resulting from "statistical noise" is also stressed. So far there are no reports on normative MTT values for 99mTc-EC, although such values were already determined for ¹³¹I-OIH, 99mTc-DTPA and 99mTc-MAG3. The aim of this study is an assessment of inter- and intraobserver reproducibility of MTT and PTT for 99mTc-EC, and determination of normative values for these parameters. MATERIALS AND METHODS: 31 patients (17 women and 14 men aged 19-75, average 44 years) referred for dynamic renal scintigraphy with: unilateral flow impairment (11), unilateral nephrolithiasis (2), control after unilateral lithotripsy (4), moderate hypertension (demographically with > 99% probability of primary hypertension) (4), suspected cirrhosis of one kidney (3), future kidney donors (3), control after abdominal injuries (3), incontinence (1). 42 functionally efficient kidneys were included in the study. Criteria for recognition of a kidney as functionally efficient were: - no earlier history of renal disease, signs of renal damage in basic blood and urine tests, or abnormalities in ultrasonography; - normal result of dynamic renal scintigraphy (in terms of sequential images and renographic curve). MTT and PTT values were determined independently by two operators, using a matrix method for deconvolution of renographic curves. RESULTS: Differences between mean MTT and PTT from two studies by one operator were insignificant and those values were closely correlated (r = 0.99 and r = 0.97, respectively). Differences of values obtained by both operators were practically insignificant for MTT (r = 0.93), and significant for PTT (r = 0.81 and p < 0.001). These differences do not disqualify that processing method. The upper limits of normative values of MTT and PTT were based on the results from first study performed by more experienced operator - 200 s and 170 s, respectively. CONCLUSIONS: The procedure of processing dynamic renal scintigraphy used in this study is reproducible. Normative values of MTT and PTT for 99mTc-EC were established as 200 s and 170 s, respectively. An attempt to optimize and standardize the technique of determining parenchymal ROI in a matrix deconvolution method, followed by an evaluation of clinical usefulness of these parameters in the diagnosis of chosen renal function impairments would be a logical continuation of this initial research.

Antioxidant changes of leek (Allium ampeloprasum var. porrum) during spontaneous fermentation of the white shaft and green leaves.

BACKGROUND: Leek is grown for its thickened cylindrical white shaft made up of long leaf bases. Despite the potentially valuable nutritional profile of the green leaves, a large portion remains unused owing its restricted culinary applications. This large quantity of this plant biomass could be valorized given an adequate stabilization method. In this study, we examined leek fermentation with regard to antioxidant changes. RESULTS: The oxygen radical absorbance capacity (ORAC) increased by 62% when the green leaves were fermented for 21 days, while 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity did not increase significantly. Fermentation resulted in an increase of endogenous polyphenolic compounds such as ferulic acid, astragalin, luteolin and naringenin. Moreover, fermentation stimulated the production of a series of polyphenolic compounds that were not present in the fresh leek. The flavour precursors in leek, i.e. methiin and isoalliin, were reduced by 91-93% and 100%, respectively, when spontaneous fermentation was allowed to occur on the white shaft and green leaves. CONCLUSION: Our results demonstrated that application of fermentation resulted in a higher ORAC value and polyphenol content of the leek plant, especially in the green leaves. These results indicate the nutritional relevance of fermentation, which hold promise as a stabilization technique.

Assessment of cerebral blood flow findings using 99mTc-ECD single-photon emission computed tomography in patients diagnosed with major depressive disorder.

BACKGROUND: Single-photon emission computed tomography (SPECT) is used as an ancillary diagnostic tool in clinical psychiatry. A variety of SPECT studies has been conducted on the findings and the factors that affect the findings, and there is a possibility that age has an effect on cerebral blood flow. We used SPECT to verify the cerebral blood flow findings of patients with major depressive disorder (MDD) considering the effect of age on the findings. METHODS: We conducted a retrospective survey of inpatients who fulfilled the DSM-IV diagnostic criteria for MDD and who had undergone imaging by technetium-99m ethyl cysteinate dimer ((99m)Tc-ECD) SPECT (N=98, 37 males). After excluding organic factors and comorbidities, we established a depression group (N=61, 24 males) and conducted an inter-group comparison with a normal control group by using SPM software considering the effect of age. RESULTS: The depression group showed the reduction of cerebral blood flow in the prefrontal area bilaterally, predominantly on the left, including the orbitofrontal cortex, anterior portion of the gyrus cinguli, and dorsolateral prefrontal area, in the left temporal lobe, and in the occipital lobe bilaterally, predominantly on the left. The findings were common to all age groups and that age-specific pattern was not detected. LIMITATIONS: The facts that this was a retrospective study and small sample size in each age group were limitations of this research. Although it also seems important to evaluate the impact of medication on cerebral blood flow and conduct an evaluation according to the subtype of depression, but we couldn't in this study. In the future it will be necessary to accumulate additional cases and conduct additional studies, including a prospective survey. CONCLUSION: The results of this study may suggest the existence of a common biological background in patients with MDD that is unaffected by age.

Preclinical assessment of the distribution, metabolism, and excretion of S-propargyl-cysteine, a novel H2S donor, in Sprague-Dawley rats.

AIM: To study the distribution, metabolism and excretion of S-propargyl-cysteine (SPRC), a novel hydrogen sulfide (H2S) donor, after oral administration in rats. METHODS: Adult Sprague-Dawley rats were used. The tissue distribution of [(35)S] SPRC-derived radioactivity was measured using a liquid scintillation counter. The plasma protein binding of SPRC was examined using 96-well equilibrium dialysis. The excretion of SPRC in urine, bile and feces was analyzed using the LC-MS/MS method. The major metabolites in rat biomatrices were identified using MRM information-dependent, acquisition-enhanced product ion (MRM-IDA-EPI) scans on API 4000QTrap system. RESULTS: After oral administration of [(35)S]-SPRC at a dose of 75 mg/kg, [(35)S] SPRC-derived radioactivity displayed broad biological distribution in various tissues of rats, including its target organs (heart and brain) with the highest in kidney. On the other hand, the binding of SPRC to human, rat and dog plasma protein was low. Only 2.18% ± 0.61% and 0.77% ± 0.61% of the total SPRC administered was excreted unchanged in the bile and urine. However, neither intact SPRC nor its metabolites were detected in rat feces. The major metabolic pathway in vivo (rat bile, urine, and plasma) was N-acetylation. CONCLUSION: The preliminary results suggest that SPRC possesses acceptable pharmacokinetic properties in rats.

Quantitative determination of S-alk(en)ylcysteine-S-oxides by micellar electrokinetic capillary chromatography.

A novel method for determination of S-alk(en)ylcysteine-S-oxides by capillary electrophoresis has been developed and validated. The method is based on extraction of these sulfur amino acids by methanol, their derivatization by fluorenylmethyl chloroformate and subsequent separation by micellar electrokinetic capillary chromatography. Main advantages of the new method are simplicity, sensitivity, high specificity and very low running costs, making it suitable for routine analysis of a large number of samples. Employing this method, the content of S-alk(en)ylcysteine-S-oxides was determined in 12 commonly consumed alliaceous and cruciferous vegetables (e.g. garlic, onion, leek, chive, cabbage, radish, cauliflower and broccoli). The total content of these amino acids in the Allium species evaluated varied between 0.59 and 12.3mg g(-1) fresh weight. Whereas alliin was found only in garlic, isoalliin was the major S-alk(en)ylcysteine-S-oxide in onion, leek, chive and shallot. On the other hand, the cruciferous species analyzed contained only methiin in the range of 0.06-2.45mg g(-1) fresh weight.

Assessment of the genotoxicity of trichloroethylene and its metabolite, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), in the comet assay in rat kidney.

Trichloroethylene (TCE) has been reported to give a small, but significant, increase in renal tumours in the rat. These tumours were always associated with nephrotoxicity which is most likely caused by the metabolism of TCE to S-(1,2-dichlorovinyl)-L-cysteine (DCVC) which accumulates in the proximal tubules. The genotoxicity of TCE and DCVC have been evaluated in vivo using the comet assay to assess DNA breakage in the proximal tubules of rat kidneys. Rats were exposed to TCE by inhalation or to DCVC by oral gavage at dose levels in excess of those which produced effects in long-term bioassays. Cell suspensions were produced from proximal tubules isolated from the kidneys of treated rats and the level of DNA damage assessed in these cells using the pH >13 comet assay. In vitro and in vivo positive controls were included and demonstrated the sensitivity of the assay. TCE gave a clearly negative response in the assay at all dose levels as did DCVC at the 16-h sampling time and at the 2-h sampling time with the lower dose level. At the 2-h sampling time following administration of DCVC at the higher dose level (10 mg/kg), there was limited evidence of DNA damage in a small number of animals, but this was considered insufficient to indicate a positive response in this assay. These data support an overall conclusion, based on these and other published data, that the renal tumours seen in bioassays are non-genotoxic in origin.

Assessment of cerebrovascular reserve before and after STA-MCA bypass surgery by SPECT and SPM analysis.

OBJECTIVE: The purpose of this study was to objectively assess the efficacy of superficial temporal artery to middle cerebral artery (STA-MCA) bypass surgery using Technetium (Tc)-99m-ethyl cysteinate dimer (ECD) single photon emission computed tomography (SPECT) in patients who underwent STA-MCA bypass surgery. MATERIALS AND METHODS: Brain perfusion SPECT images obtained at baseline and after the administration of acetazolamide were reconstructed using statistical parametric mapping in 23 patients, both before and after STA-MCA bypass surgery. The clinical outcomes of the surgery were also recorded and compared with the hemodynamic changes. A voxel with an uncorrected p-value of less than 0.001 was considered to be statistically significant. RESULTS: SPECT images of the territory supplied by the bypass graft showed an increase in both cerebrovascular flow and reserve at baseline, and the increase was significantly higher following the administration of acetazolamide. All patients showed improvement of clinical symptoms and increased blood flow to the left temporal, parietal, and frontal cortices as well as the thalamus. CONCLUSION: Brain SPECT effectively and objectively demonstrated the improved outcomes of STA-MCA bypass surgery, and thus may be used in postoperative analyses.

[Development and assessment of an automatic quantitative cerebral vascular reserve estimation tool for use with triple-injection 99mTc-ECD SPECT].

In nuclear medicine, cerebral vascular reserve(CVR) is evaluated using technetium-99m ethyl cysteinate dimer [99mTc-ECD] and acetazolamide(ACZ). We developed a protocol involving the intravenous injection of 99mTc-ECD in three divided doses(TIE method), and have found that the cerebrovascular response to ACZ depended on time after ACZ administration. However, it was difficult to obtain high-precision quantitative SPECT images by the conventional method because of complicated image processing and image degradation accompanying image subtraction. We recently developed software known as the Automatic Quantitative CVR Estimation Tool(hereinafter referred to as Triple AQCEL), which, after the input of simple parameters, enables us to carry out automatic reconstruction of quantitative SPECT images without image degradation due to subtraction. Triple AQCEL was determined to reduce image degradation caused by subtraction and to provide valid quantitative data. Because Triple AQCEL does not require manual determination of ROI or image selection for the reconstruction of quantitative SPECT images, reproducibility of regional cerebral blood flow by 3DSRT is ensured. Since all analyses in evaluation by the TIE method are automated and the operator plays no part in them, with the resulting increase of throughput, this software will contribute to improved reproducibility of regional cerebral blood flow data, and will be useful in clinical pathophysiological assessment both preoperatively and during postoperative follow-up.

Perfusion MRI before and after acetazolamide administration for assessment of cerebrovascular reserve capacity in patients with symptomatic internal carotid artery (ICA) occlusion: comparison with 99mTc-ECD SPECT.

INTRODUCTION: Impaired cerebral vascular reserve (CVR) in patients with symptomatic internal carotid artery (ICA) occlusion is regarded as a possible indication for performing extra-/intracranial (EC/IC) bypass surgery. As perfusion MR imaging (MRI) can demonstrate cerebral haemodynamics at capillary level, our hypothesis was that perfusion MRI could be used in these patients for the evaluation of CVR following acetazolamide challenge in a similar way to single photon emission CT (SPECT) and might provide additional information. METHODS: Enrolled in the study were 12 patients (mean age 61.3 years; 11 male, 1 female) with symptomatic unilateral ICA occlusion proven by angiography. Both perfusion MRI and 99m-technetium-ethyl-cysteinate dimer ((99m)Tc-ECD) SPECT were performed before and after injection of acetazolamide (Diamox ,1000 mg i.v.). CVR parameters including regional cerebral blood flow (rCBF) and volume (rCBV), and mean transit times (MTT) were measured by perfusion MRI. RESULTS: The patients with impaired CVR proven by SPECT (n = 9) had a negative mean rCBF increment (-46.52%), negative rCBV increment (-13.5%) and delayed MTT (mean +2.98 s), respectively, on the occluded side (Student's t-test all P < 0.05). The patients with sufficient CVR (n = 3) had a mean rCBF increment of 1.2%, a decrement of rCBV of 10.46%, and a mean MTT shortening of 0.27 s following the acetazolamide injection. CONCLUSIONS: Perfusion MRI before and after acetazolamide administration compares favourably with (99m)Tc-ECD SPECT for the detection of impaired CVR. The impact that perfusion MRI studies (before and after acetazolamide administration) might have on the treatment decision in patients with ICA occlusion has yet to be determined by a prospective study.

Statistical parametric mapping and statistical probabilistic anatomical mapping analyses of basal/acetazolamide Tc-99m ECD brain SPECT for efficacy assessment of endovascular stent placement for middle cerebral artery stenosis.

INTRODUCTION: Statistical parametric mapping (SPM) and statistical probabilistic anatomical mapping (SPAM) were applied to basal/acetazolamide Tc-99m ECD brain perfusion SPECT images in patients with middle cerebral artery (MCA) stenosis to assess the efficacy of endovascular stenting of the MCA. METHODS: Enrolled in the study were 11 patients (8 men and 3 women, mean age 54.2 +/- 6.2 years) who had undergone endovascular stent placement for MCA stenosis. Using SPM and SPAM analyses, we compared the number of significant voxels and cerebral counts in basal and acetazolamide SPECT images before and after stenting, and assessed the perfusion changes and cerebral vascular reserve index (CVRI). RESULTS: The numbers of hypoperfusion voxels in SPECT images were decreased from 10,083 +/- 8,326 to 4,531 +/- 5,091 in basal images (P = 0.0317) and from 13,398 +/- 14,222 to 7,699 +/- 10,199 in acetazolamide images (P = 0.0142) after MCA stenting. On SPAM analysis, the increases in cerebral counts were significant in acetazolamide images (90.9 +/- 2.2 to 93.5 +/- 2.3, P = 0.0098) but not in basal images (91 +/- 2.7 to 92 +/- 2.6, P = 0.1602). The CVRI also showed a statistically significant increase from before stenting (median 0.32; 95% CI -2.19-2.37) to after stenting (median 1.59; 95% CI -0.85-4.16; P = 0.0068). CONCLUSION: This study revealed the usefulness of voxel-based analysis of basal/acetazolamide brain perfusion SPECT after MCA stent placement. This study showed that SPM and SPAM analyses of basal/acetazolamide Tc-99m brain SPECT could be used to evaluate the short-term hemodynamic efficacy of successful MCA stent placement.

Combined 99mTc-ECD SPECT and neuropsychological studies in MCI for the assessment of conversion to AD.

Identifying pre-clinical Alzheimer's disease (AD) in subjects with mild cognitive impairment (MCI) is a major issue in clinical diagnosis. Establishing a combination of predictive markers from different fields of research might help in increasing the diagnostic accuracy. Aim of this study was to evaluate the potential role of 99mTc-ECD single photon emission computed tomography (SPECT) and memory scores in predicting conversion to AD in MCI subjects. Thirty-one MCI subjects underwent a clinical and neuropsychological examination, and a regional cerebral blood flow (rCBF) SPECT scan at baseline. Subjects had been followed periodically through 2 years in order to monitor the progression of cognitive symptoms. Canonical variate analysis of principal components was able to separate all subjects who converted to AD from those who remained stable, the former being characterized by a specific hypometabolic pattern, involving the parietal and temporal lobes, precuneus, and posterior cingulate cortex. Canonical correlation analysis of combined baseline memory deficits and rCBF SPECT images identified pre-clinical AD with a sensitivity and specificity of 77.8%. The pattern of hypoperfusion 99mTc-ECD SPECT and the severity of memory deficits predict the risk of progression to probable AD dementia in MCI subjects.

[Improvement in accuracy of quantitative assessment of the regional cerebral blood flow with 99mTc-ECD].

Mean cerebral blood flow (mCBF) in the slice including the basal ganglia (reference slice) is necessary for the quantification of regional CBF using Patlak plot and BUR methods on 99mTc-ECD cerebral perfusion SPECT. The mCBF was calculated from the mean counts of this slice. A region of interest (ROI) has been manually set on the reference slice to obtain the mean counts (manual ROI method). However, there was large variability observed in the value of rCBF in this method. We developed a 3DSRT method for improving the accuracy of the mean counts in the reference slice and evaluated the difference between the value of rCBF on manual ROI method and that on 3DSRT method in consecutive 11 patients with cerebral vascular disease. Difference in the value of mean counts of the reference slice was distributed within the 2 standard deviations (SD) with Blant-Altman analysis in 9 of 11 patients. Significant difference in the value of mean counts between two methods was observed in 2 of 11 patients. 3DSRT method is superior accuracy to the manual ROI method in the evaluation of the counts in the ROI. Lower accuracy in manual ROI method, therefore, results in the difference of the value of mean counts. 3DSRT method provides high accuracy with the various quantitative methods for the evaluation of rCBF using 99mTc-ECD.

Assessment of the optimal time interval and background region of interest in the measurement of differential renal function in Tc-99m-EC renography.

BACKGROUND: Differential renal function (DRF) measurements are routinely corrected for background, which mainly affects the reproducibility and accuracy of the measurement. The present study was conducted to identify the most appropriate background ROI and optimal time interval in the calculation of DRF for EC renography. MATERIALS AND METHODS: Nineteen patients were studied. For determination of DRF in EC renography, the selected time intervals were 0.5-1.5; 0.5-2; 1-2; 1.5-2.5; 2-3 min, and the background ROI types were inferolateral crescent, lateral crescent, and perirenal shaped. The reference DRF was obtained through DMSA study. For low functioning kidney of each patient, relative uptake differences between the DMSA and EC scans were calculated. Then, the mean differences and the standard deviations were found. RESULTS: The highest correlation was between the DRF values obtained using inferolateral background ROI in 0.5-2 minutes of EC scintigraphy and the DRF values obtained through posterior DMSA images (r = 0.9889). However, there were no statistically significant differences between the mean DRF values obtained for each time interval with each ROI type (p > 0.05). For all the time intervals and background ROIs, the mean of the differences was <0.9%. In conclusion, in obtaining comparable DRF values from EC and DMSA studies, none of the background types proved superior. Also our research for optimal time interval showed that EC scintigraphy underestimates the DRF when compared to DRF obtained from DMSA study. The DRF has a tendency to decrease as the later time intervals are used. The time intervals less than 2.5 minutes show lower underestimation of DRF values.

Detection of diffuse abnormal perfusion in SPECT using a normal brain atlas.

Visual assessment, with significant inter- or intraobserver variability, is still the norm for the evaluation of Single Photon Emission Computerized Tomography (SPECT) cerebral perfusion studies. We present in this paper an automated method for screening SPECT studies to detect diffuse disseminated abnormalities based on a computerized atlas of normal regional cerebral blood flow (rCBF). To generate the atlas, a set of normal brain SPECT studies are registered together. The atlas contains the intensity mean, the nonlinear displacement mean, and the variance of the activity pattern. A patient is then evaluated by registering his or her SPECT volume to the atlas and computing the nonlinear 3-D displacement of each voxel needed for the best shape fit to it. A voxel is counted as "abnormal" if the intensity difference between the atlas and the registered patient (or if the 3-D motion necessary to move the voxel to its registered position) is superior to 3 SD of normal mean. The number of abnormal voxels is used to classify studies. We validated this approach on 24 SPECT perfusion studies selected visually for having clear diffuse anomalies and 21 normal studies. A Markovian segmentation algorithm is also used to identify the white and gray matters for regional analysis. Based on the number of abnormal voxels, two supervised classifiers were tested: (1) minimum distance-to-mean and (2) Bayesian. The analysis of the intensity and displacement "abnormal" voxels allow one to achieve an 80% correct classification rate for the whole brain and a 93% rate if we consider only voxels in the segmented gray matter region.

Assessment of therapeutic tumor response using 99mtc-ethylenedicysteine-glucosamine.

PURPOSE: The aim of this study was to evaluate 99mTc-ethylenedicysteine-glucosamine (EC-DG) for the assessment of tumor growth. METHOD: To evaluate whether 99mTc-EC-DG is involved in cell nuclei activity, in vitro thymidine incorporation, and cell-cycle assays of EC-DG were conducted using lung and breast cancer cells. Biodistribution of 99mTc-EC-DG in lung tumor-bearing mice (0.5-4 hours, 1 Ci/mouse, i. v.) was used to estimate the radiation-absorbed dose. Autoradiograms of 99mTc-EC-DG and 18F-FDG were compared in nude mice bearing uterine sarcoma. Rabbits inoculated with VX-2 cells were imaged with 99mTc-EC-DG and 99mTc-EC. For therapeutic assessment studies, scintigraphic imaging studies with 99mTc-EC-DG in mammary tumor-bearing rats were conducted at various days after treatment with paclitaxel and cisplatin. The imaging findings were correlated immunohistochemical assays (mRNA expression, apoptosis, and cell-cycle changes in tumor), and flow cytometry analysis was performed. RESULTS: In vitro cellular uptake assays indicated that cell nuclei activity could be assessed by 99mTc-EC-DG. Scintigraphy and autoradiograms in animal models demonstrated that the tumor could be clearly visualized by 99mTc-EC-DG. The efficacy of paclitaxel and cisplatin treatment in rodent models could be assessed using tumor/muscle ratios. Immunohistochemical staining indicated a reduced expression of bFGF and an increased apoptosis and cell-cycle changes after paclitaxel and cisplatin treatment. CONCLUSION: 99mTc-EC-DG is involved in cell nuclei activity and could assess the therapeutic tumor response.