Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor.

PURPOSE: Metabolic activity and hypoxia are both important factors characterizing tumor aggressiveness. Here, we used F-18 fluoromisonidazole (FMISO) and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to define metabolically active hypoxic volume, and investigate its clinical significance in relation to progression free survival (PFS) and overall survival (OS) in glioblastoma patients. EXPERIMENTAL DESIGN: Glioblastoma patients (n = 32) underwent FMISO PET, FDG PET, and magnetic resonance imaging (MRI) before surgical intervention. FDG and FMISO PET images were coregistered with gadolinium-enhanced T1-weighted MR images. Volume of interest (VOI) of gross tumor volume (GTV) was manually created to enclose the entire gadolinium-positive areas. The FMISO tumor-to-normal region ratio (TNR) and FDG TNR were calculated in a voxel-by-voxel manner. For calculating TNR, standardized uptake value (SUV) was divided by averaged SUV of normal references. Contralateral frontal and parietal cortices were used as the reference region for FDG, whereas the cerebellar cortex was used as the reference region for FMISO. FDG-positive was defined as the FDG TNR ≥1.0, and FMISO-positive was defined as FMISO TNR ≥1.3. Hypoxia volume (HV) was defined as the volume of FMISO-positive and metabolic tumor volume in hypoxia (hMTV) was the volume of FMISO/FDG double-positive. The total lesion glycolysis in hypoxia (hTLG) was hMTV × FDG SUVmean. The extent of resection (EOR) involving cytoreduction surgery was volumetric change based on planimetry methods using MRI. These factors were tested for correlation with patient prognosis. RESULTS: All tumor lesions were FMISO-positive and FDG-positive. Univariate analysis indicated that hMTV, hTLG, and EOR were significantly correlated with PFS (p = 0.007, p = 0.04, and p = 0.01, respectively) and that hMTV, hTLG, and EOR were also significantly correlated with OS (p = 0.0028, p = 0.037, and p = 0.014, respectively). In contrast, none of FDG TNR, FMISO TNR, GTV, HV, patients' age, or Karnofsky performance scale (KPS) was significantly correlated with PSF or OS. The hMTV and hTLG were found to be independent factors affecting PFS and OS on multivariate analysis. CONCLUSIONS: We introduced hMTV and hTLG using FDG and FMISO PET to define metabolically active hypoxic volume. Univariate and multivariate analyses demonstrated that both hMTV and hTLG are significant predictors for PFS and OS in glioblastoma patients.

The usefulness of (18)F-FDG PET/CT for assessing methotrexate-associated lymphoproliferative disorder (MTX-LPD).

BACKGROUND: Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a benign lymphoid proliferation or malignant lymphoma in patients who have been treated with MTX. MTX withdrawal and observation for a short period should be considered in the initial management of patients who develop LPD while on MTX therapy. Here we evaluated the diagnostic accuracy and predictive value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for MTX-LPD. METHODS: We retrospectively investigated the cases of 15 patients clinically suspected of having MTX-LPD. A total of 324 anatomic regions (207 nodal and 117 extranodal regions) were assessed by (18)F-FDG PET/CT and by multi-detector row CT (MDCT). Each anatomic region was classified as either malignant or benign. The uptake of (18)F-FDG was assessed semi-quantitatively with the standardized uptake value maximum (SUVmax), the whole-body metabolic tumor volume (WBMTV), and the whole-body total lesion glycolysis (WBTLG) in order to investigate predictive factors of spontaneous regression after the withdrawal of MTX. RESULTS: MTX-LPD lesions were observed in 92/324 (28.4 %) regions. (18)F-FDG PET/CT showed 90.2 % sensitivity, 97.4 % specificity, and 95.4 % accuracy, values which were significantly higher than those of MDCT (59.8, 94.8, and 84.9 %, respectively. p < 0.002). After the withdrawal of MTX, 9/15 patients (60.0 %) achieved complete response (CR). The SUVmax, WBMTV and WBTLG values of the CR patients were 9.2 (range 2.8-47.1), 44.3 (range 0-362.6) ml, 181.8 (range 0-2180.9) ml, respectively, which were not significantly different from those of the non-CR patients: 10.6 (range 0-24.9), 15.7 (range 0-250.1) ml, and 97.4 (range 0-1052.1) ml. CONCLUSIONS: Although (18)F-FDG PET/CT was a useful tool to detect MTX-LPD lesions, none of the (18)F-FDG PET parameters before the withdrawal of MTX could be used to predict CR after the withdrawal of MTX.

Prognostic value of volume-based measurements on (11)C-methionine PET in glioma patients.

PURPOSE: (11)C-methionine (MET) PET is an established diagnostic tool for glioma. Studies have suggested that MET uptake intensity in the tumor is a useful index for predicting patient outcome. Because MET uptake is known to reflect tumor expansion more accurately than MRI, we aimed to elucidate the association between volume-based tumor measurements and patient prognosis. METHODS: The study population comprised 52 patients with newly diagnosed glioma who underwent PET scanning 20 min after injection of 370 MBq MET. The tumor was contoured using a threshold of 1.3 times the activity of the contralateral normal cortex. Metabolic tumor volume (MTV) was defined as the total volume within the boundary. Total lesion methionine uptake (TLMU) was defined as MTV times the mean standardized uptake value (SUVmean) within the boundary. The tumor-to-normal ratio (TNR), calculated as the maximum standardized uptake value (SUVmax) divided by the contralateral reference value, was also recorded. All patients underwent surgery (biopsy or tumor resection) targeting the tissue with high MET uptake. The Kaplan-Meier method was used to estimate the predictive value of each measurement. RESULTS: Grade II tumor was diagnosed in 12 patients (3 diffuse astrocytoma, 2 oligodendroglioma, and 7 oligoastrocytoma), grade III in 18 patients (8 anaplastic astrocytoma, 6 anaplastic oligodendroglioma, and 4 anaplastic oligoastrocytoma), and grade IV in 22 patients (all glioblastoma). TNR, MTV and TLMU were 3.1 ± 1.2, 51.6 ± 49.9 ml and 147.7 ± 153.3 ml, respectively. None of the three measurements was able to categorize the glioma patients in terms of survival when all patients were analyzed. However, when only patients with astrocytic tumor (N = 33) were analyzed (i.e., when those with oligodendroglial components were excluded), MTV and TLMU successfully predicted patient outcome with higher values associated with a poorer prognosis (P < 0.05 and P < 0.01, respectively), while the predictive ability of TNR did not reach statistical significance (P = NS). CONCLUSION: MTV and TLMU may be useful for predicting outcome in patients with astrocytic tumor.

FDG PET/CT diagnostic criteria may need adjustment based on MRI to estimate the presurgical risk of extrapelvic infiltration in patients with uterine endometrial cancer.

PURPOSE: The staging of endometrial cancer requires surgery which carries the risk of morbidity. FDG PET/CT combined with anatomical imaging may reduce the number of unnecessary lymphadenectomies by demonstrating the risk of extrapelvic infiltration. The purpose of this study was to optimize FDG PET/CT diagnostic criteria for risk assessment in endometrial cancer after first-line risk triage with MRI. METHODS: The study population comprised 37 patients who underwent curative surgery for the treatment of endometrial cancer. First, the risk of extrapelvic infiltration was triaged using MRI. Second, multiple glucose metabolic profiles of the primary lesion were assessed with FDG PET/CT, and these were correlated with the histopathological risk of extrapelvic infiltration including lymphovascular space invasion (LVSI) and high-grade malignancy (grades 2 and 3). The results of histological correlation were used to adjust FDG PET/CT diagnostic criteria. RESULTS: Presurgical assessment using MRI was positive for deep (>50 %) myometrial invasion in 17 patients. The optimal FDG PET/CT diagnostic criteria vary depending on the results of MRI. Specifically, SUVmax (≥16.0) was used to indicate LVSI risk with an overall diagnostic accuracy of 88.2 % in patients with MRI findings showing myometrial invasion. High-grade malignancy did not correlate with any of metabolic profiles in this patient group. In the remaining patients without myometrial invasion, lesion glycolysis (LG) or metabolic volume were better indicators of LVSI than SUVmax with the same diagnostic accuracy of 80.0 %. In addition, LG (≥26.9) predicted high-grade malignancy with an accuracy of 72.2 %. Using the optimized cut-off criteria for LVSI, glucose metabolic profiling of primary lesions correctly predicted lymph node metastasis with an accuracy of 73.0 %, which was comparable with the accuracy of visual assessment for lymph node metastasis using MRI and FDG PET/CT. CONCLUSION: FDG PET/CT diagnostic criteria may need adjustment based on the anatomical information provided by MRI. The optimized criteria can predict the risk of pathology-proven LVSI correctly in 83.8 % of patients before surgery, and thus would improve presurgical treatment planning.

Oligodendroglial component complicates the prediction of tumour grading with metabolic imaging.

PURPOSE: Previous radiological investigations have generally shown the superiority of metabolic imaging in distinguishing high-grade from low-grade glioma, but the presence of an oligodendroglial component may affect the diagnostic accuracy. We investigated the diagnostic accuracy of PET imaging using (11)C-methionine (MET) and (18)F-fluorodeoxyglucose (FDG) in distinguishing high-grade from low-grade glioma, in correlation with the oligodendroglial component. METHODS: The study population comprised adult patients who underwent preoperative PET imaging using both MET and FDG within 1 week and successful excision of the tumour tissue, which confirmed WHO grade II-IV glioma. We examined the tumour metabolic activity in terms of lesion-to-normal uptake ratios (L/N ratio) in both MET PET and FDG PET images. We assessed the correlation between the imaging results and the histological findings to determine the diagnostic accuracy of receiver operating characteristics (ROC) analysis in detecting high-grade tumours. RESULTS: We studied 46 patients with glioma (13 low-grade and 33 high-grade), including 26 with an oligodendroglial components. The L/N ratios of the PET images showed significantly higher metabolic activities in high-grade gliomas than in low-grade gliomas for both MET (4.29 ± 1.22 and 2.36 ± 0.72, respectively; p < 0.0001) and FDG (1.72 ± 0.91 and 0.77 ± 0.26, respectively; p = 0.0007) images, although significant overlaps in L/N ratio were observed between high-grade and low-grade gliomas. Excluding the 26 patents with an oligodendroglial component improved the separation for both MET (4.62 ± 1.14 vs. 2.16 ± 0.63; p < 0.001) and FDG (1.76 ± 0.87 vs. 0.71 ± 0.14; p < 0.05) images. The ROC analyses demonstrated the clinical utility of the metabolic radiotracers in distinguishing high-grade from low-grade gliomas, showing similar AUC values for MET (0.91) and FDG (0.92). Excluding the 26 patents with an oligodendroglial component also further improved the diagnostic accuracy for both MET (AUC 0.98), and FDG (AUC 1.00) images. The metabolic radiotracers were significantly correlated with the MIB-1 labelling index (R = 0.52, p < 0.05 for MET; R = 0.52, p < 0.05, for FDG) only in gliomas without an oligodendroglial component. CONCLUSION: For better characterization of gliomas and for risk assessment, the results of metabolic PET imaging should be revised after obtaining the pathological report, because oligodendroglial differentiation may positively influence the substrate metabolism and thus complicated the preoperative evaluation.

18F-FDG-PET/CT better localizes active spinal infection than MRI for successful minimally invasive surgery.

BACKGROUND: Surgical debridement is often required to treat spinal infections. Successful surgery requires accurate localization of the active infections, however, current imaging technique still requires surgeons' experience to narrow the surgical fields to achieve less invasive procedures. PURPOSE: To investigate the use of F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for successful surgical planning. MATERIAL AND METHODS: Nine patients with suspected spinal infection underwent magnetic resonance imaging (MRI) and FDG-PET/CT before surgery to locate active foci of infections. The spinal structures were divided into seven compartments at each intervertebral disc level for a total of 315 compartments investigated. The same classification system was used to design operating fields for histological correlation. RESULTS: FDG-PET/CT diagnosed fewer compartments as active infection (34 compartments, 10.8%) than MRI (62 compartments, 19.7%, P = 0.002). Surgical exploration was performed in 49 compartments, and demonstrated active infection in 25 compartments. The sensitivity / specificity of FDG-PET/CT was 100% / 79%, respectively, which was superior to those of MRI, 76% / 42%. Foci of active infection showed hypermetabolic activity with a SUVmax of 7.1 ± 2.6 (range, 3.0-12.7). Receiver operating characteristic (ROC) analysis indicated an optimal threshold for active spinal infection at a SUVmax of 4.2, corresponding to a sensitivity of 90.3% and specificity of 91.2%. CONCLUSION: FDG-PET/CT demonstrated limited areas of abnormality allowing accurate delineation, and is thus useful to narrow the surgical fields. Since overall diagnostic accuracy of FDG-PET/CT was superior to that of MRI, FDG-PET/CT is a useful technique to narrow the surgical field for successful less invasive surgery.

FDG-PET may predict the effectiveness of hyperbaric oxygen therapy in a patient with bisphosphonate-related osteonecrosis of the jaw: report of a case.

We report an advanced case of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in an osteoporotic patient treated with oral risedronate sodium for 2 years. An 80-year-old woman presented to our hospital complaining of pain, swelling and pus discharge in the lower alveolar ridge. Fluorine-18 labeled fluorodeoxyglucose positron emission tomography (FDG-PET) and bone scintigraphy showed definite uptake in the mandible. Under clinical diagnosis of BRONJ, we applied systematic treatments including antibiotic therapy, irrigation, cessation of bisphosphonate, hyperbaric oxygen (HBO) therapy, and debridement of necrotic bone. After pre-operative 20 sessions of HBO therapy, her clinical symptoms disappeared. SUVmax of FDG-PET decreased definitely from 4.5 to 2.5, although magnetic resonance image and bone scintigraphy did not show remarkable changes. After minor surgery with debridement of necrotic bone, she received another ten sessions of HBO therapy. After the treatment, her clinical course was excellent. In conclusion, this report demonstrates FDG-PET may predict the effect of HBO therapy in BRONJ.

¹8F-Fluoromisonidazole positron emission tomography may differentiate glioblastoma multiforme from less malignant gliomas.

PURPOSE: Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and its prognosis is significantly poorer than those of less malignant gliomas. Pathologically, necrosis is one of the most important characteristics that differentiate GBM from lower grade gliomas; therefore, we hypothesized that (18)F fluoromisonidazole (FMISO), a radiotracer for hypoxia imaging, accumulates in GBM but not in lower grade gliomas. We aimed to evaluate the diagnostic value of FMISO positron emission tomography (PET) for the differential diagnosis of GBM from lower grade gliomas. METHODS: This prospective study included 23 patients with pathologically confirmed gliomas. All of the patients underwent FMISO PET and (18)F-fluorodeoxyglucose (FDG) PET within a week. FMISO images were acquired 4 h after intravenous administration of 400 MBq of FMISO. Tracer uptake in the tumor was visually assessed. Lesion to normal tissue ratios and FMISO uptake volume were calculated. RESULTS: Of the 23 glioma patients, 14 were diagnosed as having GBM (grade IV glioma in the 2007 WHO classification), and the others were diagnosed as having non-GBM (5 grade III and 4 grade II). In visual assessment, all GBM patients showed FMISO uptake in the tumor greater than that in the surrounding brain tissues, whereas all the non-GBM patients showed FMISO uptake in the tumor equal to that in the surrounding brain tissues (p ≤ 0.001). One GBM patient was excluded from FDG PET study because of hyperglycemia. All GBM patients and three of the nine (33%) non-GBM patients showed FDG uptake greater than or equal to that in the gray matter. The sensitivity and specificity for diagnosing GBM were 100 and 100% for FMISO, and 100 and 66% for FDG, respectively. The lesion to cerebellum ratio of FMISO uptake was higher in GBM patients (2.74 ± 0.60, range 1.71-3.81) than in non-GBM patients (1.22 ± 0.06, range 1.09-1.29, p ≤ 0.001) with no overlap between the groups. The lesion to gray matter ratio of FDG was also higher in GBM patients (1.46 ± 0.75, range 0.91-3.79) than in non-GBM patients (1.07 ± 0.62, range 0.66-2.95, p ≤ 0.05); however, overlap of the ranges did not allow clear differentiation between GBM and non-GBM. The uptake volume of FMISO was larger in GBM (27.18 ± 10.46%, range 14.02-46.67%) than in non-GBM (6.07 ± 2.50%, range 2.12-9.22%, p ≤ 0.001). CONCLUSION: These preliminary data suggest that FMISO PET may distinguish GBM from lower grade gliomas.

Initial Physician Experience with [18F]Flutemetamol Amyloid PET Imaging Following Availability for Routine Clinical Use in Japan.

BACKGROUND: Brain amyloid is a neuropathological hallmark of Alzheimer's disease (AD). By visualizing brain amyloid, positron emission tomography (PET) may influence the diagnostic assessment and management of patients with cognitive impairment. OBJECTIVE: As part of a Japanese post-approval study to measure the safety of [18F]flutemetamol PET, the association of amyloid PET results with changes in diagnosis and diagnostic confidence was assessed. METHODS: Fifty-seven subjects were imaged for amyloid PET using [18F]flutemetamol at a single Japanese memory clinic. The cognitive diagnosis and referring physician's confidence in the diagnosis were recorded before and after availability of PET results. Imaging started approximately 90 minutes after [18F]flutemetamol administration with approximately 185 MBq injected. PET images were acquired for 30 minutes. RESULTS: Amyloid PET imaging led to change in diagnosis in 15/44 clinical subjects (34%). Mean diagnostic confidence increased by approximately 20%, from 73% pre-scan to 93% post-scan, and this rise was fairly consistent across the main patient subgroups (mild cognitive impairment, AD, and non-AD) irrespective of the pre-scan diagnosis and scan result. CONCLUSION: The study examined the utility of amyloid PET imaging in a Japanese clinical cohort and highlighted the use of an etiological diagnosis in the presence of the amyloid scan. [18F]Flutemetamol PET led to a change in diagnosis in over 30% of cases and to an increase in diagnostic confidence by approximately 20% consistent with other reports.

Differential SPECT activation patterns associated with PASAT performance may indicate frontocerebellar functional dissociation in chronic mild traumatic brain injury.

UNLABELLED: Patients with mild traumatic brain injury (TBI) often complain of cognitive fatigue during the chronic recovery phase. The Paced Auditory Serial Addition Test (PASAT) is a complex psychologic measure that may demonstrate subtle deficiencies in higher cognitive functions. The purpose of this study was to investigate the brain activation of regional cerebral blood flow (rCBF) with PASAT in patients with mild TBI to explore mechanisms for the cognitive fatigue. METHODS: Two groups consisting of 15 patients with mild TBI and 15 healthy control subjects underwent (99m)Tc-ethylene cysteine dimer SPECT at rest and during PASAT on a separate day. Cortical rCBF was extracted using a 3-dimensional stereotactic surface projection and statistically analyzed to identify areas of activation, which were compared with PASAT performance scores. RESULTS: Image analysis demonstrated a difference in the pattern of activation between patients with mild TBI and healthy control subjects. Healthy control subjects activated the superior temporal cortex (Brodmann area [BA] 22) bilaterally, the precentral gyrus (BA 9) on the left, and the precentral gyrus (BA 6) and cerebellum bilaterally. Patients with mild TBI demonstrated a larger area of supratentorial activation (BAs 9, 10, 13, and 46) but a smaller area of activation in the cerebellum, indicating frontocerebellar dissociation. CONCLUSION: Patients with mild TBI and cognitive fatigue demonstrated a different pattern of activation during PASAT. Frontocerebellar dissociation may explain cognitive impairment and cognitive fatigue in the chronic recovery phase of mild traumatic brain injury.

Noninvasive evaluation of coronary endothelial function following sirolimus-eluting stent implantation by using positron emission tomography.

OBJECTIVE: Several invasive studies have reported delayed reendothelialization and endothelial dysfunction following sirolimus-eluting stent (SES) implantation. We evaluated the changes in coronary endothelial function following SES implantation by using a noninvasive method that involved positron emission tomography and cold pressor testing (CPT). METHODS: The study was conducted on 14 lesions on which percutaneous coronary intervention (PCI) was successively performed. The lesions were classified into 2 groups depending on the PCI performed: the conventional PCI group, in which 7 conventional PCIs (plain old balloon angioplasty or bare-metal stents) were performed, and the SES group, in which 7 SESs were implanted. Coronary endothelial function was defined as the percent increase in the myocardial blood flow (MBF) during CPT. RESULTS: The resting MBF in the segments distal to the PCI sites did not differ between the conventional PCI and SES groups; however, the MBF significantly decreased in the SES group during CPT. CONCLUSIONS: These data suggest that SES implantation induces coronary endothelial dysfunction in the segments distal to the PCI sites.

Scatter Correction with Combined Single-Scatter Simulation and Monte Carlo Simulation Scaling Improved the Visual Artifacts and Quantification in 3-Dimensional Brain PET/CT Imaging with 15O-Gas Inhalation.

In 3-dimensional PET/CT imaging of the brain with 15O-gas inhalation, high radioactivity in the face mask creates cold artifacts and affects the quantitative accuracy when scatter is corrected by conventional methods (e.g., single-scatter simulation [SSS] with tail-fitting scaling [TFS-SSS]). Here we examined the validity of a newly developed scatter-correction method that combines SSS with a scaling factor calculated by Monte Carlo simulation (MCS-SSS). Methods: We performed phantom experiments and patient studies. In the phantom experiments, a plastic bottle simulating a face mask was attached to a cylindric phantom simulating the brain. The cylindric phantom was filled with 18F-FDG solution (3.8-7.0 kBq/mL). The bottle was filled with nonradioactive air or various levels of 18F-FDG (0-170 kBq/mL). Images were corrected either by TFS-SSS or MCS-SSS using the CT data of the bottle filled with nonradioactive air. We compared the image activity concentration in the cylindric phantom with the true activity concentration. We also performed 15O-gas brain PET based on the steady-state method on patients with cerebrovascular disease to obtain quantitative images of cerebral blood flow and oxygen metabolism. Results: In the phantom experiments, a cold artifact was observed immediately next to the bottle on TFS-SSS images, where the image activity concentrations in the cylindric phantom were underestimated by 18%, 36%, and 70% at the bottle radioactivity levels of 2.4, 5.1, and 9.7 kBq/mL, respectively. At higher bottle radioactivity, the image activity concentrations in the cylindric phantom were greater than 98% underestimated. For the MCS-SSS, in contrast, the error was within 5% at each bottle radioactivity level, although the image generated slight high-activity artifacts around the bottle when the bottle contained significantly high radioactivity. In the patient imaging with 15O2 and C15O2 inhalation, cold artifacts were observed on TFS-SSS images, whereas no artifacts were observed on any of the MCS-SSS images. Conclusion: MCS-SSS accurately corrected the scatters in 15O-gas brain PET when the 3-dimensional acquisition mode was used, preventing the generation of cold artifacts, which were observed immediately next to a face mask on TFS-SSS images. The MCS-SSS method will contribute to accurate quantitative assessments.

Postoperative assessment of hepatic asialoglycoprotein receptor function with Tc-99m GSA: the safety margin of resection size in living donor liver transplantation.

BACKGROUND: Living liver donation is associated with size-dependent complications. The resectable size and its safety margin should be defined for the safety of donors. The purpose of the present study was to determine if the current partial hepatectomies are done under the safety margin of the resectable size, by measuring asialoglycoprotein receptor (ASGPR) function of donor's remnant liver. MATERIAL AND METHODS: Seventy-four living donors (age 35±11 years) underwent Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (Tc-99m GSA) scintigraphy at postoperative week 1. We evaluated the scintigraphic results using established parameters of GSA uptake (LHL15) and its clearance from the blood pool (HH15). Based on the literature, we consider HH15 <0.55 to indicate normal ASGPR function, and 0.55£ HH15 <0.65 to indicate mild impairment. In terms of the hepatic uptake, we consider LHL15>0.93 to indicate normal ASGPR function, and 0.87< LHL15 £0.93 to indicate mild impairment. RESULTS: The average resected size was 337±170 mL, corresponding to 28±12% of the original donor's whole liver volume. No donors showed 0.65≤ HH15 or LHL15 <0.87, suggesting moderate or severely impaired ASGPR function. However, larger resection size (35-53%) was positively associated with higher HH15 values (R=0.53, p<0.001). In the range of HH15 (0.35-0.64) among present donors, higher HH15 values did not affect the regeneration volume (R=0.03, p=NS). CONCLUSIONS: Larger partial resection (≥35% of the original liver volume) may impair postsurgical ASGPR function, but smaller resection (<35%) was considered to be under the safety margin of the hepatectomy. Although mildly impaired postsurgical ASGPR function did not indicate poor prognosis, careful attention may be required for donors undergoing larger (³35%) partial resection.

Metabolic Activity of Red Nucleus and Its Correlation with Cerebral Cortex and Cerebellum: A Study Using a High-Resolution Semiconductor PET System.

UNLABELLED: The red nucleus (RN) is a pair of small gray matter structures located in the midbrain and involved in muscle movement and cognitive functions. This retrospective study aimed to investigate the metabolism of human RN and its correlation to other brain regions. METHODS: We developed a high-resolution semiconductor PET system to image small brain structures. Twenty patients without neurologic disorders underwent whole-brain scanning after injection of 400 MBq of (18)F-FDG. The individual brain (18)F-FDG PET images were spatially normalized to generate a surface projection map using a 3-dimensional stereotactic surface projection technique. The correlation between the RN and each voxel on the cerebral and cerebellar cortices was estimated with Pearson product-moment correlation analysis. RESULTS: Both right and left RNs were visualized with higher uptake than that in the background midbrain. The maximum standardized uptake values of RN were 7.64 ± 1.92; these were higher than the values for the dentate nucleus but lower than those for the caudate nucleus, putamen, and thalamus. The voxel-by-voxel analysis demonstrated that the right RN was correlated more with ipsilateral association cortices than contralateral cortices, whereas the left RN was equally correlated with ipsilateral and contralateral cortices. The left RN showed a stronger correlation with the motor cortices and cerebellum than the right RN did. CONCLUSION: Although nonspecific background activity around RNs might have influenced the correlation patterns, these metabolic relationships suggested that RN cooperates with association cortices and limbic areas to conduct higher brain functions.

FDG PET performed at thyroid remnant ablation has a higher predictive value for long-term survival of high-risk patients with well-differentiated thyroid cancer than radioiodine uptake.

PURPOSE: The predictive value of FDG PET at thyroid remnant ablation was evaluated in comparison to radioiodine uptake in high-risk patients with differentiated thyroid cancer. PATIENTS AND METHODS: One hundred forty-one patients who underwent radioiodine therapy (RIT) after total thyroidectomy and received at least 1 further RIT due to suspected metastases were retrospectively analyzed. Patients had not received RIT previously. FDG PET was performed before thyroid remnant ablation. Thyroid-stimulating hormone-stimulated serum thyroglobulin (Tg) was measured for biochemical response assessment (change of Tg between the first and second RIT, ΔTg). RESULTS: Biochemical response could be evaluated in 80 patients; survival data could be obtained for 88 patients (maximum, 124 months). Biochemical response was significantly better in patients with radioiodine-positive metastases compared with patients with radioiodine-negative metastases (median ΔTg I+, 55.8% vs I-, 112.6%; P < 0.01). Regarding survival, deaths occurred later in patients with radioiodine-positive metastases compared with radioiodine-negative patients; however, there was no significant difference regarding overall survival (I+, 61.3% vs I-, 58.2%; P > 0.05). Patients with FDG-positive metastases at thyroid remnant ablation showed a poorer biochemical response compared with patients with FDG-negative metastases (median ΔTg FDG+, 77.5% vs FDG-, 53.2%; P < 0.05), and these groups also differed significantly regarding survival (overall survival FDG+, 48.5% vs FDG-, 100%, P < 0.05). CONCLUSIONS: At thyroid remnant ablation, FDG PET is more predictive for long-term survival, whereas radioiodine uptake is more important for short-term response. FDG PET performed at thyroid remnant ablation might represent a useful tool for management of high-risk patients with differentiated thyroid cancer.

Accuracy of a method using short inhalation of (15)O-O(2) for measuring cerebral oxygen extraction fraction with PET in healthy humans.

UNLABELLED: PET with short inhalation of (15)O-O(2) provides regional oxygen extraction fraction (OEF) in a shorter acquisition time and with less radiation exposure than does the steady-state method. The purpose of this study was to test the accuracy of the short-inhalation technique for estimating OEF in healthy human volunteers. METHODS: The final study population included 16 healthy volunteers, who underwent a series of dynamic PET scans consisting of short inhalation of (15)O-CO, short inhalation of (15)O-O(2), and a bolus infusion of (15)O-H(2)O to generate parametric images for cerebral blood volume (CBV), cerebral blood flow (CBF), OEF, and metabolic rate of oxygen (CMRO(2)). About 45 min before PET emission scanning, arterial and jugular blood was sampled through a catheter inserted in a radial artery and the right jugular bulb, respectively. PET-derived OEF (OEFpet) of the whole brain was compared with OEF calculated from the arteriovenous blood-sampling technique (OEFav). RESULTS: Whole-brain-averaged CBF (mean +/- SD) measured with PET was 0.40 +/- 0.06 (range, 0.30-0.55) mL/g/min, CBV was 0.05 +/- 0.01 (range, 0.04-0.09) mL/g, CMRO(2) was 2.85 +/- 0.39 (range, 2.35-3.84) mL/100 g/min, and OEFpet was 0.39 +/- 0.06 (range, 0.30-0.51). OEFpet showed a slightly higher value than did OEFav (0.36 +/- 0.05 [range, 0.29-0.46]), but the difference was not significant. The difference in the 2 measurements (OEFpet - OEFav) did not correlate with CBF (r = -0.16; P = not statistically significant [NS]), CBV (r = -0.20; P = NS), CMRO(2) (r = -0.16; P = NS), partial arterial oxygen pressure (r = 0.29; P = NS) or partial arterial carbon dioxide pressure (r = -0.17; P = NS). CONCLUSION: Compared with the arteriovenous blood-sampling technique, a technique using short inhalation of (15)O-O(2) did not significantly over- or underestimate global OEF in healthy human volunteers. The PET technique reasonably estimated the cerebral OEF in local brain tissues of healthy human volunteers.

Acute changes in regional cerebral (18)F-FDG kinetics in patients with traumatic brain injury.

UNLABELLED: During the acute phase after traumatic brain injury (TBI), the metabolic state is regionally heterogeneous. The purpose of this study was to characterize contusional, pericontusional, and remote regions of TBI by estimating glucose transporter and hexokinase activities on the basis of (18)F-FDG kinetic modeling. METHODS: A standard 2-compartment model was used to measure (18)F-FDG kinetic parameters in 21 TBI patients with cerebral contusions studied during the acute phase (3.1 +/- 2.1 [mean +/- SD] d after injury). Nineteen patients also underwent (15)O-water PET to measure regional cerebral blood flow (CBF). A control study ((18)F-FDG and (15)O-water) was done with 18 healthy volunteers. The rate constants K(i), K(1), and k(3) were assumed to represent the uptake, transport, and hexokinase activity of (18)F-FDG, respectively; K(i) was calculated as K(1) x [k(3)/(k(2) + k(3))]. RESULTS: The areas of contusional and pericontusional tissues located 4.5, 13.5, and 22.5 mm away from the contusion (PC(4.5), PC(13.5), and PC(22.5), respectively) demonstrated significantly reduced K(1) values, whereas the K(1) values for remote areas remained normal. The k(3) values were significantly reduced regardless of the distance from the contusion. Pericontusional areas with CT- or MRI-evidenced tissue damage showed significantly lower K(i) (P < 0.001), CBF (P < 0.01), and K(1) (P < 0.0001) values than did areas without such damage, whereas the k(3) values did not differ significantly. Seven patients showed regionally increased (18)F-FDG uptake (hot spots) in pericontusional areas. The k(3) value for the hot spots (0.086 +/- 0.024/min) was significantly higher than that for the remote cortex (P < 0.01), whereas the K(i), CBF, and K(1) values did not show significant differences. Patients with hot spots showed significantly higher K(i) and k(3) values in PC(4.5) (P < 0.05) and higher k(3) values in PC(22.5) (P < 0.05) than did patients without hot spots, whereas the K(1) and CBF values did not differ significantly. CONCLUSION: Brain tissue (18)F-FDG kinetics in TBI patients were consistent with reduced hexokinase activity in the whole brain (including apparently uninjured cortex), whereas glucose transport was impaired only in the area immediately around the contusion. Pericontusional high levels of (18)F-FDG uptake observed in a subgroup of patients could have been the result of regionally increased hexokinase activity.

Correlation of regional metabolic rates of glucose with glasgow coma scale after traumatic brain injury.

UNLABELLED: After traumatic brain injury (TBI), subcortical white matter damage may induce a functional disconnection leading to a dissociation of regional cerebral metabolic rate of glucose (CMRglc) between the cerebral cortex and deeper brain regions. Therefore, thalamic and brain stem CMRglc may have a closer correlation than does the cerebral cortex with depth of coma after TBI. METHODS: Eleven adult healthy volunteers and 23 adult patients with TBI (median initial Glasgow Coma Scale score [GCSini], 8) underwent (18)F-FDG PET within 5 d after injury. The CMRglc of cortical areas (remote from hemorrhagic lesions), striatum, thalamus, brain stem, cerebellar cortex, and whole brain was compared with severity of injury and the level of consciousness evaluated using GCSini and the Glasgow Coma Scale score at the time of PET (GCSpet). RESULTS: The regional CMRglc of the brain stem is relatively unaffected by the TBI. Compared with healthy volunteers, TBI patients exhibited significantly depressed CMRglc in the striatum (3.9 +/- 1.3 vs. 5.1 +/- 0.9 mg/100 g/min, P < 0.05) and thalamus (3.1 +/- 1.0 vs. 4.3 +/- 0.9 mg/100 g/min, P < 0.05). CMRglc levels were not statistically lower in the cerebellum (2.9 +/- 0.8 vs. 3.5 +/- 0.8 mg/100 g/min, P = NS) and brain stem (2.5 +/- 0.5 vs. 2.6 +/- 0.5 mg/100 g/min, P = NS). However, compared between comatose and noncomatose patients, CMRglc values in the thalamus (2.7 +/- 0.7 vs. 3.6 +/- 1.2 mg/100 g/min, P < 0.05), brain stem (2.2 +/- 0.4 vs. 2.8 +/- 0.5 mg/100 g/min, P < 0.01), and cerebellar cortex (2.6 +/- 0.5 vs. 3.4 +/- 1.0 mg/100 g/min, P < 0.05) were significantly lower in comatose patients. When individual values of regional CMRglc were plotted against posttraumatic level of consciousness, CMRglc values for the thalamus, brain stem, and cerebellum significantly correlated with the level of consciousness at the time of PET (r = 0.58, P < 0.01; r = 0.66, P < 0.01; r = 0.64, P < 0.01, respectively). CT or MRI findings were normal for the analyzed structures except for 3 patients with diffuse axonal injury of the brain stem. The presence of shear injury was associated with poor GCSini (P < 0.05.) but was not related to GCSpet and brain stem CMRglc. CONCLUSION: A PET investigation using (18)F FDG demonstrated a significant difference in glucose metabolism in the thalamus, brain stem, and cerebellum between comatose and noncomatose patients acutely after TBI. The metabolic rate of glucose in these regions significantly correlated with the level of consciousness at the time of PET.

Selective metabolic reduction in gray matter acutely following human traumatic brain injury.

The aim of this study was to determine whether the apparent loss of overall gray-white matter contrast (GM/WM) seen on FDG-PET imaging reflects the differential changes of glucose metabolic rate (CMRglc) in cortical gray mater (GM) and subcortical white mater (WM) following TBI. The clinical significance of the CMRglc GM-to-WM ratio was also evaluated. Nineteen normal volunteers and 14 TBI patients were studied. Each subject had a quantitative FDG-PET, a quantitative H215O-PET and a MR scan acutely following TBI. Stabilities of the global and regional FDG lumped constants (LC) were studied. Parametric images (pixel unit: mg/min/100g) of FDG uptake rate (CURFDG) and CMRglc were generated. The changes of CMR(glc) in whole brain, GM and WM were studied separately by using a MRI-segmentation-based technique. The GM-to-WM ratios of both CURFDG and CMRglc images were significantly (p < 0.001) decreased (>31%) in TBI patients. The global LC value reduced significantly (p < 0.01) in TBI patients. The CMRglc decreased significantly (p < 0.001) in GM but not in WM (p > 0.1). Kinetic analysis revealed significant (p < 0.001) decrease of GM hexokinase activity in TBI patients. The GM-to-WM ratios of CMRglc correlated (r = 0.64) with the initial Glasgow Coma Score (GCS) of TBI patients. The patients with higher CMRglc GM-to-WM ratios (>1.54) showed good recovery 12 months after TBI. There was a selective CMRglc reduction in cortical GM following TBI. The pathophysiological basis for the reduction in GM-to-WM CMRglc ratio seen on FDG-PET imaging following TBI remains to be determined.