Parametric Cerebrovascular Reserve Images Using Acetazolamide (99m)Tc-HMPAO SPECT: A Feasibility Study of Quantitative Assessment.

PURPOSE: Basal/acetazolamide stress (99m)Tc-HMPAO single-photon emission computed tomography (SPECT) has been widely used for evaluation of hemodynamics; however, qualitative and subjective visual assessment of cerebrovascular reserve (CVR) has been performed in clinical settings. The aim of this study was to generate parametric CVR images and evaluate its feasibility of quantification. METHODS: Basal/acetazolamide stress (99m)Tc-HMPAO SPECT data from 17 patients who underwent bypass surgery or percutaneous transluminal angioplasty were used. Spatial normalization was performed and parametric CVR images were generated using relative CVR (rCVR) of each voxel proportional to CVR of the whole brain. Binary parametric maps to show area of relatively reduced CVR were generated also using threshold of rCVR < 90 %. We calculated rCVR of internal carotid artery (ICA) using the parametric CVR images and probabilistic maps for ICA territory. Pre- and postprocedural parametric CVR images were obtained and quantitative rCVRs were compared. The rCVRs were evaluated according to visual grades for regional decreased CVR. RESULTS: Postprocedural rCVR obtained from parametric CVR images increased significantly from preprocedural rCVR. The rCVR was significantly correlated with visual grades of reduced CVR for each side of ICA territories. CONCLUSIONS: We generated parametric CVR images for basal/acetazolamide stress (99m)Tc-HMPAO SPECT. As a quantitative measurement, rCVR obtained from the parametric image was feasibly assessed hemodynamic abnormalities with preserved anatomical information.

The assessment of breast cancer response to neoadjuvant chemotherapy: comparison of magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography.

BACKGROUND: Neoadjuvant chemotherapy for locally advanced breast cancer is a widely accepted treatment. For assessment of the tumor response after chemotherapy, both magnetic resonance imaging (MRI) and (18)F-fluorodeoxyglucose positron emission tomography (PET) are promising methods. PURPOSE: To retrospectively compare MRI and PET in the assessment of tumor response to neoadjuvant chemotherapy for primary breast cancer with the pathologic response as the reference standard. MATERIAL AND METHODS: Between August 2006 and May 2008, 32 women with breast cancer underwent concurrent MRI and PET before and after neoadjuvant chemotherapy. For response assessment, we calculated the changes in the maximum diameters of the tumor (ΔD(max)) on MRI, and the changes in the standard uptake values (ΔSUV) on PET. The correlation between the ΔD(max) and ΔSUV was analyzed using Pearson's correlation coefficient. The correspondence rates between each imaging modality and pathologic assessment were calculated. For prediction of the pathologic complete response (pCR), the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were analyzed using the McNemar test. RESULTS: The pathologic assessment of tumor response to neoadjuvant chemotherapy identified eight complete responses (25.0%), 10 partial responses (31.2%), and 14 non-responses (43.8%). The change in size on MRI was moderately correlated with the change in SUV on PET (r=0.574, p=0.001). The correspondence rate of response assessment was 75.0% (24/32) between MRI and pathologic response and 53.1% (17/32) between PET and pathologic response. For the pCR, specificity (95.8% vs. 62.5%) and PPV (83.3% vs. 47.1%) were statistically higher on MRI than PET (p < 0.05), while sensitivity (100.0% vs. 62.5%) and NPV (100.0% vs. 88.5%) on PET tended to be higher than MRI. CONCLUSION: Before and after neoadjuvant chemotherapy for breast cancer, the ΔD(max) of MRI correlated moderately with the ΔSUV on PET. For prediction of the pCR, MRI proved to be a more specific modality than PET.

18F-FDG PET in the assessment of tumor grade and prediction of tumor recurrence in intracranial meningioma.

PURPOSE: The purpose of this study was to investigate the role of (18)F-fluorodeoxyglucose (FDG) PET in detecting high-grade meningioma and predicting the recurrence in patients with meningioma after surgical resection. METHODS: Fifty-nine patients (27 men and 32 women) with intracranial meningioma who underwent preoperative FDG PET and subsequent surgical resection were enrolled. All patients underwent clinical follow-up for tumor recurrence with a mean duration of 34+/-20 months. The tumor to gray matter ratio (TGR) of FDG uptake was calculated and a receiver-operating characteristic (ROC) curve of the TGR was drawn to determine the cutoff value of the TGR for detection of high-grade meningioma. Further, univariate analysis with the log-rank test was performed to assess the predictive factors of meningioma recurrence. RESULTS: The TGR in high-grade meningioma (WHO grade II and III) was significantly higher than that in low-grade ones (WHO grade I) (p=0.002) and significantly correlated with the MIB-1 labeling index (r=0.338, p=0.009) and mitotic count of the tumor (r=0.284, p=0.03). The ROC analysis revealed that the TGR of 1.0 was the best cutoff value for detecting high-grade meningioma with a sensitivity of 43%, specificity of 95%, and accuracy of 81%. Of 59 patients, 5 (9%) had a recurrent event. In the log-rank test, the TGR, MIB-1 labeling index, presence of brain invasion, and WHO grade were significantly associated with tumor recurrence. The cumulative recurrence-free survival rate of patients with a TGR of 1.0 or less was significantly higher than that of patients with a TGR of more than 1.0 (p=0.0003) CONCLUSION: FDG uptake in meningioma was the significant predictive factor of tumor recurrence and significantly correlated with the proliferative potential of the tumor.

Role of [18F]FDG PET/CT in the assessment of suspected recurrent ovarian cancer: correlation with clinical or histological findings.

PURPOSE: To evaluate the accuracy of integrated positron emission tomography (PET) and computed tomography (CT) for depiction of suspected recurrent ovarian carcinoma after treatment, with use of clinical or histological findings as the reference standard. METHODS: Seventy-seven women (median age, 51 years) with ovarian carcinoma treated with primary cytoreductive surgery followed by platinum-based combination chemotherapy were included, and [18F]fluorodeoxyglucose (FDG) PET/CT was performed for suspected recurrence. In all patients, imaging findings were compared with results of histological examination after surgical exploration or clinical follow-up to determine the diagnostic accuracy of PET/CT in the evaluation of disease status. Fisher's exact test was used to measure the ability of PET/CT to predict recurrent lesions. RESULTS: Forty-five (58.4%) of the 77 patients had documented recurrence during surgical exploration or clinical follow-up, while 32 (41.6%) had no evidence of recurrent tumour. Of the 45 patients with recurrent disease, 27 (60%) were confirmed to have recurrence by surgical biopsy. A correlation was found between PET/CT and histological or clinical analyses (kappa = 0.894). The overall sensitivity, specificity, accuracy, positive predictive value and negative predictive value of PET/CT were 93.3%, 96.9%, 94.8%, 97.7% and 91.2%, respectively. PET/CT modified the diagnostic or treatment plan in 19 (24.7%) patients, by leading to the use of previously unplanned therapeutic procedures in 11 (57.9%) patients and the avoidance of previously planned diagnostic procedures in eight (42.1%) patients. CONCLUSION: Integrated FDG PET/CT is a sensitive post-therapy surveillance modality for the detection of recurrent ovarian cancer; it aids decisions on treatment plans and may ultimately have a favourable impact on prognosis.

Changes in the heterogeneity of cerebral glucose metabolism with healthy aging: quantitative assessment by fractal analysis.

BACKGROUND AND PURPOSE: It has been shown that heterogeneity of cerebral glucose metabolism is increased in neuropsychiatric degenerative diseases. However, proper assessment of older patients requires knowledge about the effect of aging on heterogeneity. This study characterized the effects of aging on the heterogeneity of the distribution of cerebral glucose metabolism in healthy volunteers. METHODS: Sixty-six healthy volunteers (age range, 19-75 years) underwent flurodeoxyglucose brain positron emission tomography (PET), and all the PET images were spatially normalized onto a previously segmented standard brain template to parcel the brain regions automatically. Fractal dimension was regarded as a quantitative measurement for the heterogeneity of cerebral glucose metabolism and obtained for 9 brain regions. Participants were subdivided into young/midlife and elderly groups, and the Student t test was applied to the comparison of fractal dimensions in those groups. Analysis of covariance was performed for each region to explore the effects of age, gender, age-by-gender interaction, and total counts in the brain on the observed metabolic heterogeneity. RESULTS: Fractal dimensions were higher for elderly volunteers in most brain regions. Differences between the 2 groups in fractal dimension emerged within the whole gray matter, temporal lobe, striatum, and cingulate. No significant gender differences, age-by-gender interactions, or total counts were observed. Significant age effects were observed in the whole gray matter, frontal lobe, temporal lobe, striatum, and cingulate gyrus. CONCLUSIONS: Heterogeneity in the cerebral glucose metabolism of healthy volunteers increased with age, and individual variations of heterogeneity were higher in older volunteers. However, there was no significant difference between male and female volunteers of the same age. The effect of age on heterogeneity was not regionally uniform.

Efficacy assessment of cerebral arterial bypass surgery using statistical parametric mapping and probabilistic brain atlas on basal/acetazolamide brain perfusion SPECT.

UNLABELLED: The efficacy of cerebral arterial bypass surgery was assessed on brain perfusion SPECT using statistical parametric mapping (SPM) and a probabilistic brain atlas. METHODS: Fifteen patients with ischemia in the internal carotid artery (ICA) territory and 21 age-matched healthy volunteers were enrolled. (99m)Tc-HMPAO basal/acetazolamide brain perfusion SPECT was performed 2 wk before and after bypass surgery and also on a healthy control group. Using SPM analysis, group comparisons were made between pre- and postoperative SPECT for each basal/acetazolamide image, and improvements of perfusion and perfusion reserve were assessed. The number of significant voxels on the SPM analysis was defined as the extent of ischemia. With the use of the probabilistic brain atlas, the counts for the cerebral lobes and the ICA territory were automatically calculated for each image and compared. RESULTS: The group comparisons by SPM between patients and healthy volunteers showed a significant improvement in general perfusion status in the ICA territory. The improvement in perfusion reserve was more extensive than the improvement in perfusion. The extent of ischemia was also significantly decreased after surgery (1,693 +/- 2,604 to 371 +/- 523 voxels in basal images, P = 0.060; 11,879 +/- 6,449 to 5,997 +/- 3,864 voxels in acetazolamide images, P = 0.005). In the analysis using the probabilistic brain atlas, the preoperatively decreased perfusion was normalized after surgery, but a residual decrease in the perfusion reserve was also observed in the ICA territory. The counts in the volume of interest of the ICA territory were significantly improved (38.5 +/- 4.1 to 41.5 +/- 2.7 in basal images, P = 0.024; 34.2 +/- 4.4 to 38.8 +/- 2.9 in acetazolamide images, P = 0.003). One patient showing a decrease in perfusion had a perioperative cerebral infarct. CONCLUSION: Using SPM and a probabilistic brain atlas, the perfusion, the perfusion reserve, and changes in both after cerebral arterial bypass surgery were effectively assessed and correlated well with physiologic reasoning.

Preparation of (188) Re-labeled paper for treating skin cancer.

For homogeneous delivery of beta radiation to skin cancer, we developed a simple method for preparing (188) Re-labeled nitrocellulose paper. The homogeneity and stability of the labeled paper were investigated. Absorbed dose estimates were calculated using the Monte-Carlo method. A 74-MBq (188) Re-labeled paper with 1-cm diameter delivered 147.2 Gy up to 1-mm depth after 2-h irradiation. Animal experiments on tumor-bearing mice showed that 50 Gy is an adequate dose for treating skin cancer. Tumors disappeared 7 days after irradiation in all the groups irradiated by 50 or 100 Gy. The (188) Re-labeled paper provided a convenient, economical, effective, and non-invasive method of treating skin cancer.

Comparison of the cost-effectiveness of stress myocardial SPECT and stress echocardiography in suspected coronary artery disease considering the prognostic value of false-negative results.

BACKGROUND: The prognoses of patients with false-negative test results by myocardial single photon emission computed tomography (SPECT) and by stress echocardiography are known to be different; the prognosis with false-negative SPECT is better in suspected and proven coronary artery disease (CAD). METHODS AND RESULTS: Three strategies by which to diagnose CAD were compared for their cost-effectiveness when considering the prognostic value of false-negative results: (1) stress myocardial SPECT by dipyridamole or adenosine followed by coronary angiography (CAG), (2) exercise stress echocardiography followed by CAG, and (3) dobutamine stress echocardiography followed by CAG. Delta quality-adjusted life-year (QALY) was calculated for the three strategies separately when annual mortality and infarction rates were 0.5% and 0.5% for myocardial SPECT and 2% and 2% for stress echocardiography, respectively. Costs were estimated and costs per DeltaQALY were calculated according to the pretest likelihood of CAD (pCAD). The myocardial SPECT followed by CAG strategy was the most cost-effective in the patients with a pCAD of 0.3 or greater, and the dobutamine echocardiography followed by CAG strategy was the most cost-effective in patients with a pCAD of 0.2 or lower. This was the case when we assumed that the nondiagnostic test rate of dobutamine echocardiography was 9% (in contrast to 0% by myocardial SPECT and 18% by exercise echocardiography). Sensitivity analysis showed that the cost-effectiveness of dobutamine echocardiography followed by CAG was best only if the prognosis of false-negative results of dobutamine echocardiography was better. The cost-effectiveness of exercise echocardiography was dubious because of the high nondiagnostic rate with inadequate exercise. CONCLUSIONS: When the lower event rates of (false) negative SPECT were considered, the relatively expensive myocardial SPECT strategy was more cost-effective than the cheaper stress echocardiography strategy in patients with a pCAD of 0.3 or greater. According to sensitivity analysis, the prognostic value of false-negative results and the nondiagnostic test rate were important determinants of stress myocardial study cost-effectiveness.

Consideration of perfusion reserve in viability assessment by myocardial Tl-201 rest-redistribution SPECT: a quantitative study with dual-isotope SPECT.

BACKGROUND: To optimize the use of thallium 201 rest-redistribution study in Tl-201/technetium 99m sestamibi dual-isotope single photon emission computed tomography (SPECT), the predictability of Tl-201 rest-redistribution for viable myocardium was examined according to the degree of perfusion reserve. METHODS AND RESULTS: Twenty patients with both unstable angina and left ventricular dysfunction were enrolled. Tl-201 rest-dipyridamole stress Tc-99m sestamibi gated SPECT/Tl-201 24-hour redistribution SPECT was performed before and 3 months after coronary artery bypass grafting. Through use of a 20-segment model, segmental stress perfusion, rest perfusion, and systolic thickening were quantified on gated SPECT by means of automatic quantitation software. Perfusion was expressed as the average percentage of maximal radioactivity uptake. To represent perfusion reserve, the perfusion difference score (PDS) was defined as rest perfusion minus stress perfusion. A low PDS indicated little or no inducible ischemia, and a high PDS indicated inducible ischemia. In dysfunctional myocardium, viability was defined by the improvement of thickening after coronary artery bypass grafting. The overall predictability of Tl-201 redistribution for viability was 0.709 of the area under the curve (AUC) in receiver operating characteristic analysis. With a cutoff of 7, predictability was significantly better in the low PDS group (AUC = 0.785) than in the high PDS group (AUC = 0.582). CONCLUSIONS: The predictability of Tl-201 rest-redistribution for viability differs according to perfusion reserve. It was more reliable for dysfunctional myocardium with persistent perfusion decrease. On the basis of the continuum hypothesis of chronic stunning and hibernation, we suggest that dysfunctional myocardium with persistent perfusion decrease should be assessed by Tl-201 redistribution SPECT.

Diagnostic Accuracy of F-18 FDG-PET in the Assessment of Posttherapeutic Recurrence of Head and Neck Cancer.

The purpose of this study was to compare whole-body fluorine-18-fluorodeoxyglucose positron emission tomography (F-18 FDG-PET) with conventional imaging modalities (CI: CT/MRI) in the detection of recurrent head and neck cancer. Whole-body F-18 FDG-PET was performed in 45 patients (recurrence = 39; no recurrence = 16) with previous head and neck cancer. We compared detectability by the period from initial cancer treatment and treatment modalities. Thirty were PET-positive and 15 were PET-negative. The sensitivity, specificity, and accuracy of PET were 97%, 88%, and 93%, respectively (corresponding figures of CI were 73%, 85%, and 77%). In 18 patients who underwent PET less than 3 months after the completion of cancer treatment, the sensitivity, specificity, and accuracy were 100%, 86%, and 94%, while for CI, the corresponding figures were 67%, 71%, and 69%. In 18 patients who had undergone surgery, PET results were 14 true positive and 4 were true negative; significantly higher detectability than CI. Among the patients who were evaluated for more than 6 months or treated by radiotherapy without surgery, diagnostic accuracy was almost the same. Whole body F-18 FDG-PET was a valuable tool in the evaluation of post-therapeutic recurrence of head and neck cancer.