Yoshifumi Sugawara

Preclinical and clinical studies of bone marrow uptake of fluorine-1-fluorodeoxyglucose with or without granulocyte colony-stimulating factor during chemotherapy.

PURPOSE To evaluate the effect of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on bone marrow glucose metabolism in rodents and in patients, as assessed by 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) uptake measured directly or by positron-emission tomography (PET) scanning. MATERIALS AND METHODS Groups of three rats received either daily saline, G-CSF, or GM-CSF injections for 7 days. After treatment, FDG was injected and F-18 activities in tissues measured 1 hour later. Twenty-two breast cancer patients treated with multiagent chemotherapy were sequentially studied with PET. Eleven patients received G-CSF therapy as an adjunct to chemotherapy, while 11 received chemotherapy only. The standardized uptake value-lean (SUL) of bone marrow FDG uptake was measured and compared. RESULTS In rats, bone marrow F-18 activity was significantly higher in both CSF groups than in the saline group (G-CSF, 0.44 +/- 0.08; GM-CSF, 0.33 +/- 0.02; saline, 0.18 +/- 0.02% injected dose [ID]/g x kg; P < .05), but the other normal tissues had comparable biodistributions to controls. In breast cancer patients, the FDG uptake of bone marrow did not change with chemotherapy alone; however, marrow uptake was increased after treatment with G-CSF. The dose of G-CSF and duration of treatment were correlated with the extent of increase in FDG uptake. The SUL of bone marrow was as follows: baseline, 1.56 +/- 0.23; after one cycle, 3.13 +/- 1.40 (P < .01); after two cycles, 2.22 +/- 0.85 (P < .05); and after three cycles, 2.14 +/- 0.79 (P < .05), respectively. Although the FDG uptake of bone marrow declined after G-CSF treatment was completed, it was higher than the baseline level for up to 4 weeks postcompletion of G-CSF and the elevated marrow FDG uptake was sustained longer than the period of blood neutrophil count elevation. CONCLUSION Substantial increases in bone marrow FDG uptake are rapidly induced by CSF treatments and should not be misinterpreted as diffuse bone marrow metastases.

Cardiac imaging using 256-detector row four-dimensional CT: preliminary clinical report

PurposeAlong with the increase of detector rows on the z-axis and a faster gantry rotation speed, the spatial and temporal resolutions of the multislice computed tomography (CT) have been improved for noninvasive coronary artery imaging. We investigated the feasibility of the second specification prototype 256-detector row four-dimensional CT for assessing coronary artery and cardiac function.Materials and methodsThe subjects were five patients with coronary artery disease. Contrast medium (40–60 ml) was intravenously administered at the rate of 3–4 ml/s. The patients whole heart was scanned for 1.5 s to cover at least one cardiac cycle during breathholding without electrocardiographic gating. Parameters used were 0.5 mm slice thickness, 0.5 s/rotation, 120 Kv, and 350 mA, with a half-scan reconstruction algorithm (temporal resolution 250 ms). Twenty-six transaxial datasets were reconstructed at intervals of 50 ms.ResultsThe assessability of the coronary arteries in AHA segments 1, 2, 3, 5, 6, 7, 9, and 11 was visually evaluated, resulting in 29 of 32 (90.9%) segments being assessable. Functional assessment was also performed using animated movies without banding artifacts in all cases.ConclusionsThe 256-detector row four-dimensional CT can assess the coronary artery and cardiac function using data during 1.5 s without banding artifacts.

Local Control of Metastatic Lung Tumors Treated with SBRT of 48 Gy in Four Fractions: In Comparison with Primary Lung Cancer

OBJECTIVE The optimal dose of stereotactic body radiotherapy (SBRT) for metastatic lung tumors has not been clarified. Local control rates of metastatic lung tumors treated with SBRT of 48 Gy in four fractions, which is one of the common dose schedules for Stage I primary lung cancer in Japan, were examined. METHODS Between 2006 and 2008, 12 metastatic lung tumors (colorectal cancer, 7; others, 5) in 10 patients and 56 lesions of Stage I primary lung cancer (T1, 43; T2, 13) in 52 patients were treated with SBRT of 48 Gy in four fractions at the isocenter. RESULTS Two-year overall survival rates were 86% for patients with metastatic lung tumors and 96% for patients with Stage I primary lung cancer (P = 0.4773). One- and 2-year local control rates were 48% and 25% for metastatic lung tumors, and 91% and 88% for Stage I primary lung cancer, respectively (P < 0.0001). CONCLUSIONS The local control rates after SBRT of 48 Gy in four fractions were significantly worse in metastatic lung tumors compared with Stage I primary lung cancer. In SBRT, metastatic lung tumors should be clearly differentiated from primary lung cancer and should be given higher doses.

Improvement of brain single photon emission tomography (SPET) using transmission data acquisition in a four-head SPET scanner.

Attenuation coefficient maps (μ-maps) are a useful way to compensate for non-uniform attenuation when performing single photon emission tomography (SPET). A new method was developed to record single photon transmission data and aμ-map for the brain was produced using a four-head SPET scanner. Transmission data were acquired by a gamma camera opposite to a flood radioactive source attached to one of four gamma cameras in the four-head SPET scanner. Attenuation correction was performed using the iterative expectation maximization algorithm and theμ-map. Phantom studies demonstrated that this method could reconstruct the distribution of radioactivity more accurately than conventional methods, even for a severely non-uniformμ-map, and could improve the quality of SPET images. Clinical application to technetium-99m hexamethylpropylene amine oxime (HMPAO) brain SPET also demonstrated the usefulness of this method. Thus, this method appears to be promising for improvement in the image quality and quantitative accuracy of brain SPET.

Heterogeneity of cerebral blood flow in frontotemporal lobar degeneration and Alzheimer’s disease

This study was designed to quantify the heterogeneity on cerebral blood flow single-photon emission tomography (SPET) images in frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD) using a three-dimensional fractal analysis. Twenty-one FTLD patients, 21 AD patients and 11 healthy controls underwent technetium-99m hexamethylpropylene amine oxime SPET scanning. Patients with FTLD and AD matched for sex, age and the severity of dementia as estimated with the Clinical Dementia Rating and were determined to be in the early stage of illness. We delineated the SPET images using a 35% cut-off and a 50% cut-off of the maximal voxel radioactivity and measured the number of voxels included in the contours of two different cut-offs. The fractal dimension (FD) was calculated by relating the logarithms of the cut-offs and the numbers of voxels, and it was defined as the heterogeneity of the cerebral perfusion. We divided the SPET images into two sets, anterior and posterior, with equal numbers of coronal SPET slices. We calculated total FD, anterior FD and posterior FD for total, anterior and posterior SPET images. Anterior FDs for FTLD and AD were 1.55±0.34 and 1.24±0.19 (P=0.0002). The ratios of anterior to posterior FD for FTLD and AD were 1.81±0.41 and 1.32±0.14 (P<0.0001). Use of the anterior FD and the ratio of anterior to posterior FD separated FTLD patients from AD patients and controls with a sensitivity of 85.7% and a specificity of 93.8%. Anterior FD and the ratio of anterior to posterior FD may be useful in distinguishing FTLD from AD.

Does the FDG Uptake of Primary Non-Small Cell Lung Cancer Predict Prognosis?. A Work in Progress.

OBJECTIVE: To determine if the intensity of fluorine-18-fluorodeoxyglucose (FDG) uptake in primary non-small cell lung cancer (NSCLC) could independently predict patient prognosis.METHODS: Thirty-eight patients with untreated NSCLC were studied with FDG-PET. Primary tumor FDG uptake was calculated by the standardized uptake value based on lean body mass (SUV-lean). Cumulative survival rate and the SUV-lean were compared.RESULTS: There were no significant differences between the tumor stages and the SUV-lean. Although the survival rates significantly decreased as the stage progressed (p =.0049), there was no significant difference in the survival rate between the group with lower primary tumor FDG uptake (SUV-lean </= 8.72) and the group with higher tumor FDG uptake (SUV-lean > 8.72) (p =.2256). However, in the subset of patients without metastasis, survival tended to be longer with a lower tumor SUV-lean.CONCLUSION: In this population of patients with NSCLC, the tumor FDG uptake does not independently predict the prognosis.

Ischemic “memory image” in acute myocardial infarctio of123I-BMIPP after reperfusion therapy: A comparison with99mTc-pyrophosphate and201Tl dual-isotope SPECT

Ischemic “memory image” is a phenomenon of123I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) in which an area at risk of acute myocardial infarction (AMI), could be detected as a defect in a couple of weeks even after successful reperfusion therapy.The purpose of this study was to clarify the incidence of the ischemic “memory image” of123I-BMIPP in patients with AMI by comparing99mTc-PYP and201Tl dual-isotope SPECT.Materials consisted of 14 patients with successfully reperfused AMI and 20 patients with old myocardial infarction (OMI). All AMI patients underwent PYP/Tl dual-isotope SPECT within 1 week after the onset of AMI, and BMIPP SPECT was performed within 1 week after the PYP/Tl dual-isotope SPECT. The extent and severity of the defect of BMIPP and Tl were visually scored into four grades: 0=no defect to 3=large or severe defect. These scores were compared.PYP positive AMI lesions were concordant with BMIPP defects (13/14). In AMI, both the extent and severity scores of BMIPP were higher than201Tl (p<0.001). Differences (BMIPP-Tl) of extent and severity scores were greater in AMI than in OMI (p<0.001).In conclusion, the ischemic “memory image” obtained by means of the BMIPP is a common phenomenon (13/14) in AMI, and helpful in evaluating the area at risk.

Relationship between Pretreatment FDG Uptake and Local Control after Stereotactic Body Radiotherapy in Stage I Non-small-cell Lung Cancer: The Preliminary Results

OBJECTIVE Relationship between pretreatment uptake of (18)F-fluoro-2-deoxy-d-glucose and local control after stereotactic body radiotherapy in stage I non-small-cell lung cancer was examined. METHODS Between June 2006 and June 2009, 90 clinically diagnosed stage I primary lung cancer in 86 patients were treated with stereotactic body radiotherapy in Shikoku Cancer Center. Among these, 51 tumors in 51 patients were evaluated by positron emission tomography using (18)F-fluoro-2-deoxy-d-glucose before treatment. Twenty-six tumors of histopathologically confirmed non-small-cell lung cancer were reviewed in this study. Tumors were divided into two groups by the threshold maximum standardized uptake value of 5.0 (high-uptake tumors, 9; low-uptake tumors, 17). One tumor with low uptake was pure ground-glass opacity. Typically, 48 Gy in four fractions was given at the isocenter. RESULTS Follow-up time was 4-44 months (median, 21 months). Local failure-free rates at 15 months of the high-uptake group and the low-uptake group were 40% and 93% for all tumors (P= 0.0001), 0% and 91% for tumors 3 cm or less (P= 0.0004), 50% and 100% for tumors larger than 3 cm, and 40% and 89% for the mainly solid tumors (P= 0.0010). There were no statistically significant differences of local failure-free rates according to age, sex and tumor size (P= 0.4804, P= 0.4170 and P= 0.3638, respectively). CONCLUSIONS High uptake of (18)F-fluoro-2-deoxy-d-glucose in a primary tumor was the significant unfavorable factor for local control after stereotactic body radiotherapy in stage I non-small-cell lung cancer.

Regional cerebral blood flow change in a case of Alzheimer's disease with musical hallucinations

We examined alteration of regional cerebral blood flow (rCBF) in a case of Alzheimers disease (AD) patient with musical hallucination. To detect regions related to musical hallucination, single–photon emission computed tomography (SPECT) imaging of the patient and nine sex, age, and cognitive functionmatched AD patients without delusions and hallucinations were compared using statistical parametric mapping 99 (SPM99). In comparison with controls, the patient had increased rCBF in left temporal regions and left angular gyrus. This profile could be relevant to the neuroanatomical basis of musical hallucinations.

Measurement of tumor blood flow using dynamic contrast-enhanced magnetic resonance imaging and deconvolution analysis : A preliminary study in musculoskeletal tumors

Objective: To measure tumor blood flow (TBF) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Methods: A DCE-MRI was performed using inversion recovery-preparation fast-field echo sequences. Dynamic data were obtained every 3.2 seconds for 2 minutes, immediately after gadolinium injection. In 14 patients with malignant musculoskeletal tumors, TBF maps were generated pixel-by-pixel by deconvolution analysis. For preclinical studies, muscle blood flow in 5 volunteers and signal intensities of different gadolinium concentrations were measured. Results: There was a good linear relationship between signal intensities and gadolinium concentrations (r = 0.989, P < 0.001, at gadolinium concentrations ≤2 mmol/L). The average value of muscle blood flow in volunteers was 11.1 ± 2.7 mL·100 mL−1·min−1. In 14 patients with musculoskeletal tumors, TBF showed wide variances: the lowest of 9.6 mL·100 mL−1·min−1 in liposarcoma and the highest of 182.0 mL·100 mL−1·min−1 in osteosarcoma. After chemotherapy, the TBF values (7.9, 11.0, and 11.7 mL· 100 mL−1·min−1) in the good responders were lower than those (26.8, 31.0, and 62.4 mL·100 mL−1·min−1) in the poor responders. Conclusions: A functional map of TBF generated by DCE-MRI and deconvolution analysis would be a promising tool for evaluating tumor blood flow in vivo.