Shingo Baba

CT Hounsfield Units of Brown Adipose Tissue Increase with Activation: Preclinical and Clinical Studies

Brown adipose tissue (BAT) densities assessed as CT Hounsfield units (HUs) were evaluated in a rodent model and in patients to determine whether HUs changed in relation to BAT activity. Methods: Serial 18F-FDG PET/CT was performed on rats under both room temperature control conditions and after 4 h of cold-stimulation, which is known to activate BAT. The maximum standardized uptake values and CT HUs of BAT were measured, and tissues were examined in the laboratory. Image records from cancer patients who underwent PET/CT were reviewed, and 23 patients were identified who displayed both high and low 18F-FDG uptake into BAT on serial 18F-FDG PET/CT scans. The maximum standardized uptake values and CT HUs of BAT were compared in these scans. Results: The mean (±SD) CT HUs of cold-activated BAT (−12.4 ± 22.4) were significantly higher than those (−27.9 ± 9.6) of the controls in the rat model. The CT HUs of BAT (−71.6 ± 18.0) in the patients with high 18F-FDG uptake were significantly higher than those (−104.4 ± 16.8) of the patients with low 18F-FDG uptake . A decrease in relative lipid content is seen in activated BAT in rats on histology. Conclusion: The CT HUs of BAT increased in activated conditions in both animals and patients, likely because of lipid consumption by activated BAT.

Improvement in PET/CT Image Quality with a Combination of Point-Spread Function and Time-of-Flight in Relation to Reconstruction Parameters

The aim of this study was to investigate the effects of the point-spread function (PSF) and time-of-flight (TOF) on improving 18F-FDG PET/CT images in relation to reconstruction parameters and noise-equivalent counts (NEC). Methods: This study consisted of a phantom study and a retrospective analysis of 39 consecutive patients who underwent clinical 18F-FDG PET/CT. The body phantom of the National Electrical Manufacturers Association and International Electrotechnical Commission with a 10-mm-diameter sphere was filled with an 18F-FDG solution with a 4:1 radioactivity ratio compared with the background. The PET data were reconstructed with the baseline ordered-subsets expectation maximization (OSEM) algorithm, with the OSEM+PSF model, with the OSEM+TOF model, and with the OSEM+PSF+TOF model. We evaluated image quality by visual assessment, the signal-to-noise ratio of the 10-mm sphere (SNR10 mm), the contrast of the 10-mm sphere, and the coefficient of variance in the phantom study and then determined the optimal reconstruction parameters. We also examined the effects of PSF and TOF on the quality of clinical images using the signal-to-noise ratio in the liver (SNRliver) in relation to the NEC in the liver (NECliver). Results: In the phantom study, the SNR10 mm was the highest for the OSEM+PSF+TOF model, and the highest value was obtained at iteration 2 for algorithms with the TOF and at iteration 3 for those without the TOF. In terms of a postsmoothing filter full width at half maximum (FWHM), the high SNR10 mm was obtained with no filtering or was smaller than 2 mm for algorithms with PSF and was 4–6 mm for those without PSF. The balance between the contrast recovery and noise is different for algorithms with either PSF or TOF. A combination of PSF and TOF improved SNR10 mm, contrast, and coefficient of variance, especially with a small-FWHM gaussian filter. In the clinical study, the SNRliver of the low-NECliver group in the OSEM+PSF+TOF model was compared with that of the high-NECliver group in conventional OSEM. The PSF+TOF improved the SNRliver by about 24.9% ± 9.81%. Conclusion: A combination of PSF and TOF clearly improves image quality, whereas optimization of the reconstruction parameters is necessary to obtain the best performance for PSF or TOF. Furthermore, this combination has the potential to provide good image quality with either lower activity or shorter acquisition time, thus improving patient comfort and reducing the radiation burden.

Comparison of18FDG-PET with99mTc-HMDP scntigraphy for the detection of bone metastases in patients with breast cancer

ObjectiveBone is one of the most common sites of metastasis in breast cancer patients. Although bone scintigraphy is widely used to detect metastatic breast cancer, the usefulness of18FDG-PET for detecting bone metastasis has not been clearly evaluated. The purpose of this study was to compare the diagnostic accuracy of18FDG-PET with bone scintigraphy in detecting bone metastasis in breast cancer patients.MethodsForty-four women aged 35 to 81 years (mean, 56 years) with breast cancer were examined in this study. Both18FDG-PET and bone scintigraphy were performed for each patient with 0-69 day intervals (mean, 11.5 days). The results of each image interpretation were compared retrospectively. Whole-body bones were classified into 9 anatomical regions. Metastases were confirmed at 45/187 regions in 14 patients by bone biopsy or clinical follow-up including other imaging techniques for a period of at least 6 months afterwards.ResultsOn a region basis, the sensitivity, specificity, and accuracy of18FDG-PET were 84%, 99% and 95%, respectively. Although these results were comparable to those of bone scintigraphy, the combination of18FDG-PET and bone scintigraphy improved the sensitivity (98%) and accuracy (97%) of detection. False negative lesions of bone scintigraphy were mostly bone marrow metastases and those of18FDG-PET were mostly osteoblastic metastases.18FDG-PET was superior to bone scintigraphy in the detection of osteolytic lesions (92% vs. 73%), but inferior in the detection of osteoblastic lesions (74% vs. 95%).ConclusionsThis study shows that18FDG-PET tends to be superior to bone scintigraphy in the detection of osteolytic lesions, but inferior in the detection of osteoblastic lesions.18FDG-PET should play a complementary role in detecting bone metastasis with bone scintigraphy.

Assessment of Interobserver Reproducibility in Quantitative 18F-FDG PET and CT Measurements of Tumor Response to Therapy

Our goal was to estimate and compare across different readers the reproducibility of the 18F-FDG PET standardized uptake value (SUV) and CT size measurements, and changes in those measurements, in malignant tumors before and after therapy. Methods: Fifty-two tumors in 25 patients were evaluated on 18F-FDG PET/CT scans. Maximum SUVs (SUVbw max) and CT size measurements were determined for each tumor independently on pre- and posttreatment scans by 8 different readers (4 PET, 4 CT) using routine nonautomated clinical methods. Percentage changes in SUVbw max and CT size between pre- and posttreatment scans were calculated. Interobserver reproducibility of SUVbw max, CT size, and changes in these values were described by intraclass correlation coefficients (ICCs) and estimates of variance. Results: The ICC was higher for the pretreatment, posttreatment, and percentage change in SUVbw max than the ICC for the longest CT size and the 2-dimensional CT size (before treatment, 0.93, 0.72, and 0.61, respectively; after treatment, 0.91, 0.85, and 0.45, respectively; and percentage change, 0.94, 0.70, and 0.33, respectively). The variability of SUVbw max was significantly lower than the variability of the longest CT size and the 2-dimensional CT size (mean ± SD before treatment, 6.3% ± 14.2%, 16.2% ± 17.8%, and 27.5% ± 26.7%, respectively, P ≤ 0.001; and after treatment, 18.4% ± 26.8%, 35.1% ± 47.5%, and 50.9% ± 51.4%, respectively, P ≤ 0.02). The variability of percentage change in SUVbw max (16.7% ± 36.2%) was significantly lower than that for percentage change in the longest CT size (156.3% ± 157.3%, P ≤ 0.0001) and the 2-dimensional CT size (178.4% ± 546.5%, P < 0.0001). Conclusion: The interobserver reproducibility of SUVbw max for both untreated and treated tumors and percentage change in SUVbw max are substantially higher than measurements of CT size and percentage change in CT size. Measurements of tumor metabolism by PET should be included in trials to assess response to therapy. Although PET reproducibility was high, the variability observed in analyses of identical image sets by 4 readers indicates that automated analytic tools to assess response might be helpful to further enhance reproducibility.

Diagnostic and Prognostic Value of Pretreatment SUV in 18F-FDG/PET in Breast Cancer: Comparison with Apparent Diffusion Coefficient from Diffusion-Weighted MR Imaging

In oncology, the apparent diffusion coefficient (ADC) measured by diffusion-weighted MR imaging (DWI) and the standardized uptake value (SUV) from 18F-FDG PET have similar clinical applications. The purpose of this study was to assess the correlation between the ADC and SUV and compare their potential in the diagnosis and prediction of prognosis in breast tumors. Methods: Seventy-nine female patients (age range, 19–69 y; average, 49.1 y) with 83 pathologically proven breast tumors were recruited. The diagnoses consisted of 70 malignant breast tumors (65 cases of invasive ductal carcinoma, 1 of medullary carcinoma, 1 of mucinous carcinoma, 1 of squamous cell carcinoma, and 2 of micropapillary carcinoma) and 13 benign breast tumors (4 cases of fibroadenoma, 4 of mastopathy, 3 of adenosis with atypia, and 2 of benign phyllodes tumor). All patients underwent mammary gland MR imaging with DWI and 18F-FDG PET within a 2-wk interval. The patients’ ADCs and SUVs were measured within the tumor by DWI and 18F-FDG PET, respectively. For the malignant tumors, we evaluated the relationships among ADC, SUV, histopathologic appearance, and long-term prognosis. Results: A significant difference (P < 0.05) was observed in both parameters (ADC and SUV) between the benign and malignant breast tumors, and the difference was more significant when we introduced a new parameter, SUV/ADC. There was a weak inverse correlation between ADC and SUV (r = −0.36; P = 0.06) among the total tumors; however, this correlation was not significant within the group of malignant tumors. High SUV was found to correlate with larger tumor size, higher nuclear grade, and the triple-negative hormonal receptor profile. High ADC was revealed to be correlated with negative progesterone receptor and positive human epidermal growth factor receptor 2 profile. Higher SUVs also showed a correlation with poor prognosis. No correlation was seen between ADC and prognosis. Conclusion: Both SUV and ADC are helpful parameters in differentiating benign from malignant breast tumors. The use of SUV and ADC in combination may help in the diagnosis because of their inverse relationship. High preoperative SUV was associated with poor prognosis, but the contribution of ADC to prognosis prediction was small.

Influences of point-spread function and time-of-flight reconstructions on standardized uptake value of lymph node metastases in FDG-PET

PURPOSE The purpose of this study was to investigate the effects of point-spread function (PSF) and time-of-flight (TOF) on the standardized uptake value (SUV) of lymph node metastasis in FDG-PET/CT. MATERIALS AND METHODS This study evaluated 41 lymph node metastases in 15 patients who had undergone (18)F-FDG PET/CT. The lesion diameters were 2.5 cm or less. The mean short-axis diameter of the lymph nodes was 10.5 ± 3.7 mm (range 4.6-22.8mm). The PET data were reconstructed with baseline OSEM algorithm, with OSEM+PSF, with OSEM+TOF and with OSEM+PSF+TOF. A semi-quantitative analysis was performed using the maximum and mean SUV of lymph node metastases (SUVmax and SUVmean) and mean SUV of normal lung tissue (SUVlung). We also evaluated image quality using the signal-to-noise ratio in the liver (SNRliver). RESULTS Both PSF and TOF increased the SUV of lymph node metastases. The combination of PSF and TOF increased the SUVmax by 43.3% and the SUVmean by 31.6% compared with conventional OSEM. By contrast, the SUVlung was not influenced by PSF and TOF. TOF significantly improved the SNRliver. CONCLUSION PSF and TOF both increased the SUV of lymph node metastases. Although PSF and TOF are considered to improve small-lesion detectability, it is important to be aware that PSF and TOF influence the accuracy of quantitative measurements.

A single-strand conformation polymorphism method for the large-scale analysis of mutations/polymorphisms using capillary array electrophoresis

We present a high‐throughput single‐strand conformation polymorphism (SSCP) method, performed on a commercially available capillary array DNA sequencer. We tested various sieving matrices and electrophoretic conditions, using 51 DNA fragments which included 45 fragments carrying only one single nucleotide polymorphism (SNP), 4 fragments having two SNPs and 2 fragments with insertion or deletion. Resolution of alleles was improved by increasing concentrations of both sieving matrices and buffers, and all examined polymorphisms of DNA fragments were detected, most of them (45 fragments) as clearly split allele peaks in heterozygotes. Allele frequencies of SNPs can be estimated accurately by determining the relative amounts of alleles in pooled DNA. In this method, the turn‐around time for the analysis of 96 samples is less than 3 h. These results demonstrate that capillary array‐based SSCP is an efficient and accurate technique for the large‐scale quantitative analysis of mutations/polymorphisms.

Hyperbaric oxygenation prevents delayed neuronal death following transient ischaemia in the gerbil hippocampus

The mechanism of the neuroprotective effect of hyperbaric oxygenation remains unclear although its clinical benefits have been well recognized for human ischaemic neuronal disease. The preventive effect of hyperbaric oxygenation against delayed neuronal death was investigated in the gerbil following transient forebrain ischaemia. Delayed neuronal death in the gerbil was produced by clips on both the common carotid arteries (10 min). Morphological examination was carried out after several protocols of hyperbaric oxygenation, modified from the protocols for human ischaemic neuronal disease. Neurons in the hippocampal CA1 were well preserved in the gerbils treated with hyperbaric oxygenation, more so than in the gerbils with no hyperbaric oxygenation. Moreover, more neurons were preserved in the CA1 treated with hyperbaric oxygenation within 6 h of the ischaemia, than when the hyperbaric oxygenation was started 24 h after the ischaemia. The induction of heat shock proteins (HSP72 and HSP27) became weaker in the gerbils with hyperbaric oxygenation than in those without hyperbaric oxygenation, as seen immunohistochemically. We also observed an increase in dense bodies, that were shown to be lysosomes and myelinoid structures in the cytoplasm of the neurons ultrastructurally, in the hippocampus with hyperbaric oxygenation. However, no oxygen toxicity to the neurons was detected, up to at least two atmospheres absolute. This experimental system was useful to investigate the preventive mechanism of hyperbaric oxygenation against delayed neuronal death in the gerbil, and to determine the clinical indications and the most effective protocol for hyperbaric oxygenation for ischaemic neuronal damage in the human brain.

Pulmonary tumor thrombotic microangiopathy: FDG-PET/CT findings.

Pulmonary tumor thrombotic microangiopathy (PTTM) is histopathologically characterized by proliferation of intimal myofibroblasts in the small pulmonary arterioles, induced by tumor microemboli. Patients develop rapidly progressive and severe cardiopulmonary failure, and the clinical course of this disease is fatal. Conventional radiologic findings are often minimal or nonspecific, making diagnosis difficult before death. We report 2-(F-18)-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) images of PTTM, which illustrate the characteristic findings of this clinical entity. FDG-PET can be helpful for the diagnosis of PTTM.

How Reproducible Is Bioluminescent Imaging of Tumor Cell Growth? Single Time Point versus the Dynamic Measurement Approach:

To determine the most robust and reproducible parameters for noninvasively estimating tumor cell burden in a murine model, we used real-time in vivo bioluminescent imaging to assess the growth kinetics and dissemination of luciferase-transfected Raji B-cell lymphoma. Bioluminescent signals were acquired every minute for 40 minutes after luciferin injection every other day post-tumor injection. The total 40-minute area under the curve (AUC) of photon intensity (photons/second) was calculated and compared with simplified fixed time point observations (every 5 minutes from 5 to 40 minutes after substrate injection). There was substantial variability in the shape of the time signal intensity curves at different stages of tumor growth in both the intravenous and subcutaneous models. The coefficient of variance in the AUC was 0.27 (intravenous) and 0.36 (subcutaneous) as values determined by fitting the curve, whereas the 20-minute time point measurement varied at 0.29 (intravenous) and 0.37 (subcutaneous). In both the subcutaneous and intravenous models, single time point measurements at 20 minutes had the highest correlation value with AUC. This simplified single time point measurement appears appropriate to estimate the total tumor burden in this model, but the substantial variance at each measurement must be considered in experimental designs.