Changes In Fluorodeoxyglucose Uptake Research Articles

Improvement of liver metabolic activity in people with advanced HIV after antiretroviral therapy initiation.

Objective:Evaluating hepatic metabolic changes in people with HIV (PWH) with advanced disease, before and after antiretroviral therapy (ART) initiation, using [18F]-fluorodeoxyglucose (FDG) PET-computed tomography (PET/CT). FDG PET/CT noninvasively quantifies glucose metabolism in organs.Design/methods:Forty-eight viremic PWH (CD4+ cell counts <100 cells/μl) underwent FDG PET/CT at baseline and approximately 6 weeks after ART initiation (short-term). Twenty-seven PWH participants underwent follow-up scans 2 years after treatment (long-term). FDG PET/CT scans from 20 healthy controls were used for comparison. Liver FDG uptake was quantified from the PET/CT scans. Imaging findings as well as clinical, laboratory, and immune markers were compared longitudinally and cross-sectionally to healthy controls.Results:Liver FDG uptake was lower at baseline and short-term in PWH compared with controls (P < 0.0001). At the long-term scan, liver FDG uptake of PWH increased relative to baseline and short-term (P = 0.0083 and 0.0052) but remained lower than controls’ values (P = 0.004). Changes in FDG uptake correlated negatively with levels of glucagon, myeloperoxidase, sCD14, and MCP-1 and positively with markers of recovery (BMI, albumin, and CD4+ cell counts) (P < 0.01). In multivariable analyses of PWH values across timepoints, BMI and glucagon were the best set of predictors for liver FDG uptake (P < 0.0001).Conclusion:Using FDG PET/CT, we found decreased liver glucose metabolism in PWH that could reflect hepatocytes/lymphocytes/myeloid cell loss and metabolic dysfunction because of inflammation. Although long-term ART seems to reverse many hepatic abnormalities, residual liver injury may still exist within 2 years of treatment initiation, especially in PWH who present with low nadir CD4+ cell counts.

Positron emission tomography and magnetic resonance imaging in experimental human malaria to identify organ-specific changes in morphology and glucose metabolism: A prospective cohort study.

Plasmodium vivax has been proposed to infect and replicate in the human spleen and bone marrow. Compared to Plasmodium falciparum, which is known to undergo microvascular tissue sequestration, little is known about the behavior of P. vivax outside of the circulating compartment. This may be due in part to difficulties in studying parasite location and activity in life. To identify organ-specific changes during the early stages of P. vivax infection, we performed 18-F fluorodeoxyglucose (FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) at baseline and just prior to onset of clinical illness in P. vivax experimentally induced blood-stage malaria (IBSM) and compared findings to P. falciparum IBSM. Seven healthy, malaria-naive participants were enrolled from 3 IBSM trials: NCT02867059, ACTRN12616000174482, and ACTRN12619001085167. Imaging took place between 2016 and 2019 at the Herston Imaging Research Facility, Australia. Postinoculation imaging was performed after a median of 9 days in both species (n = 3 P. vivax; n = 4 P. falciparum). All participants were aged between 19 and 23 years, and 6/7 were male. Splenic volume (P. vivax: +28.8% [confidence interval (CI) +10.3% to +57.3%], P. falciparum: +22.9 [CI -15.3% to +61.1%]) and radiotracer uptake (P. vivax: +15.5% [CI -0.7% to +31.7%], P. falciparum: +5.5% [CI +1.4% to +9.6%]) increased following infection with each species, but more so in P. vivax infection (volume: p = 0.72, radiotracer uptake: p = 0.036). There was no change in FDG uptake in the bone marrow (P. vivax: +4.6% [CI -15.9% to +25.0%], P. falciparum: +3.2% [CI -3.2% to +9.6%]) or liver (P. vivax: +6.2% [CI -8.7% to +21.1%], P. falciparum: -1.4% [CI -4.6% to +1.8%]) following infection with either species. In participants with P. vivax, hemoglobin, hematocrit, and platelet count decreased from baseline at the time of postinoculation imaging. Decrements in hemoglobin and hematocrit were significantly greater in participants with P. vivax infection compared to P. falciparum. The main limitations of this study are the small sample size and the inability of this tracer to differentiate between host and parasite metabolic activity. PET/MRI indicated greater splenic tropism and metabolic activity in early P. vivax infection compared to P. falciparum, supporting the hypothesis of splenic accumulation of P. vivax very early in infection. The absence of uptake in the bone marrow and liver suggests that, at least in early infection, these tissues do not harbor a large parasite biomass or do not provoke a prominent metabolic response. PET/MRI is a safe and noninvasive method to evaluate infection-associated organ changes in morphology and glucose metabolism.

Brain activation patterns during visuomotor adaptation in motor experts and novices: An FDG PET study with unrestricted movements

BackgroundSpeed of performance improvements and the strength of memory consolidation in humans vary with movement expertise. Underlying neural mechanisms of behavioural differences between levels of movement expertise are so far unknown. New methodIn this study, PET with [18F]fluorodeoxyglucose (FDG) was proposed as a powerful novel methodology to assess learning-related brain activity patterns during large non-restricted movements (ball throwing with a right hand). 24 male handball players (‘Experts’) and 24 male participants without handball experience (‘Novices’) performed visuomotor adaptations to prismatic glasses with or without strategic manoeuvres (i.e., explicit or implicit adaptation). ResultsRegional changes in FDG uptake as a marker of neuronal activity, relative to a control condition, were assessed. Prismatic adaptation, in general, was associated with decreased occipital neuronal activity as a possible response to misleading visual information. In ‘Experts’, the adaptation was associated with altered neuronal activity in a network comprising the right parietal cortex and the left cerebellum. In ‘Novices’, implicit adaptation resulted in an activation of the middle frontal and inferior temporal gyrus. Comparison with existing methodsThis study demonstrates the versatility of FDG PET for studying brain activations patterns in experimental settings with unrestricted movements that are not accessible by other techniques (e.g., fMRI or EEG). ConclusionsObserved results are consistent with the involvement of different functional networks related to strategic manoeuvres and expertise levels. This strengthens the assumption of different mechanisms underlying behavioural changes associated with movement expertise. Furthermore, the present study underscores the value of FDG PET for studying brain activation patterns during unrestricted movements.

Fluorodeoxyglucose Detected Changes in Brain Metabolism After Chemotherapy in Pediatric Non-Hodgkin Lymphoma

BackgroundPotential neurocognitive dysfunction after chemotherapy is a worrisome long-term outcome. Our objective was to evaluate the effect on brain metabolism in pediatric patients with non–central nervous system cancer treated with chemotherapy by analyzing brain data from serial whole-body fluorodeoxyglucose positron emission tomography/computed-tomography (FDG-PET/CT) scans taken before and sequentially after therapy. MethodsFourteen pediatric patients diagnosed with lymphoma and treated with systemic and prophylactic intrathecal chemotherapy were included. All patients had baseline pretreatment whole-body FDG-PET/CT and at least one post-therapy study preformed as part of standard surveillance. Brain positron emission tomography data were quantitatively analyzed for normalized fluorodeoxyglucose uptake in various brain regions. A generalized estimating equation approach was used to evaluate temporal changes after chemotherapy. ResultsMedian time of follow-up surveillance positron emission tomography–computed-tomography was 456 days after chemotherapy course. Various brain regions demonstrated significant changes in fluorodeoxyglucose uptake as a function of time passed since chemotherapy. Increased fluorodeoxyglucose uptake was noted in the parietal and cingulate cortexes. Decreased fluorodeoxyglucose uptake was demonstrated in deep gray matter nuclei and in the brainstem. ConclusionsOur study provides novel insights into long-standing and progressive changes in regional glucose metabolism after chemotherapy in pediatric cancer population, lasting long after the end of therapy and reaching clinical remission. Expanding the utility of regular surveillance fluorodeoxyglucose positron emission tomography to a detailed quantitative assessment of regional brain metabolism after chemotherapy can provide valuable information on individual chemotherapy-related neuromodulation and facilitate the development of strategies to minimize neurocognitive side effects.

Correlation Between Standardized Uptake Value in Preneoadjuvant and Postneoadjuvant Chemoradiotherapy and Tumor Regression Grade in Patients With Locally Advanced Esophageal Cancer.

To investigate whether positron emission tomography/computed tomography (PET/CT) initial and restaging imaging predicts for pathologic response measured by tumor regression grade (TRG) after preoperative chemoradiotherapy (CRT) in patients with locally advanced esophageal cancer. A retrospective review of 220 patients with stage II-III esophageal cancer treated with neoadjuvant CRT followed by surgery was performed. In total, 187 patients were eligible for statistical analysis. Pretreatment and posttreatment PET/CT scans were reviewed. Maximum standard uptake value (SUV) at the site of the primary tumor was recorded before and 6 weeks after neoadjuvant therapy. Upon completion of surgery, TRG was determined by a specialized site-specific gastrointestinal pathologist. Spearman correlation was used to compare pre, post, and change in maximum SUV, TRG, and overall survival. The median follow-up was 24 months. Although no significant correlation was found between pretreatment SUV and TRG (r=0.073, P=0.32), post-CRT SUV, however, showed a significant positive correlation with TRG (r=0.374, P<0.01). There was no significant correlation between the absolute change in fluorodeoxyglucose uptake after CRT and TRG (r=0.057, P=0.44); however, the rate of SUV change showed a significant correlation with TRG (r=0.178, P=0.017). Similar to previous studies, our study showed a significant difference in overall survival between TRG groups (log-rank test, P=0.019). Patients with TRG 3 showed prominently worse survival with median survival of 27.4 months. Patients with favorable pathologic responses were those whose scans demonstrated a metabolic response defined as a decrease in SUV≥70%. Changes in SUV uptake on PET/CT scans after CRT have prognostic value in predicting pathologic response of esophageal cancer after neoadjuvant therapy. Further studies are needed to validate the integration of PET/CT as a decision-making tool.

Early cortical metabolic rearrangement related to clinical data in idiopathic sudden sensorineural hearing loss

Results in studies concerning cortical changes in idiopathic sudden sensorineural hearing loss (ISSNHL) are not homogeneous, in particular due to the different neuroimaging techniques implemented and the diverse stages of ISSNHL studied. Considering the recent advances in state-of-the-art positron emission tomography (PET) cameras, the aim of this study was to gain more insight into the neuroanatomical differences associated with the earliest stages of unilateral ISSNHL and clinical-perceptual performance changes.After an audiological examination including the mean auditory threshold (mean AT), mean speech discrimination score (mean SDS) and Tinnitus Handicap Inventory (THI), 14 right-handed ISSNHL patients underwent brain [18F]fluorodeoxyglucose (FDG)-PET within 72 h of the onset of symptoms. When compared to an homogeneous group of 35 healthy subjects by means of statistical parametric mapping, a relative increase in FDG uptake was found in the right superior and medial frontal gyrus as well as in the right anterior cingulate cortex in ISSNHL patients. Conversely, the same group showed a significant relative decrease in FDG uptake in the right middle temporal, precentral and postcentral gyrus as well as in the left posterior cingulate cortex, left lingual, superior, middle temporal and middle frontal gyrus and in the left insula. Regression analysis showed a positive correlation between mean THI and glucose consumption in the right anterior cingulate cortex and a positive correlation between mean SDS and glucose consumption in the left precentral gyrus.The relative changes in FDG uptake found in these brain regions and the positive correlation with mean SDS and THI scores in ISSNHL could possibly highlight new aspects of cerebral rearrangement, contributing to further explain changes in those functions that support speech recognition during the sudden impairment of unilateral auditory input.

Cerebral glucose metabolism on positron emission tomography of children

Establishing the normative range of age-dependent fluorodeoxyglucose (FDG) uptake in the developing brain is necessary for understanding regional quantitative analysis of positron emission tomography (PET) brain images in children and also to provide functional information on brain development. We analyzed head sections of FDG PET/computed tomography (CT) images for 115 patients (5 months to 23 years) without central nervous system disease before treatment, as PET studies are not performed on healthy children owing to ethical considerations and the risk of radiation exposure. We investigated the changes in FDG uptake and established age-associated normative ranges of cerebral FDG. Head sections of FDG PET/CT images were registered to a population-based probabilistic atlas of human cortical structures. Gray matter of 56 brain structures was defined on normalized PET images according to the atlas. To avoid individual and experimental confounding factors, the relative standardized uptake value (SUV) over the cerebellum of each structure was calculated. Relative SUVs were analyzed by ANOVA and modeled using generalized estimating equalization analysis with false discovery rate control. Age and structure were significant factors affecting SUVs. Anatomic proximity had little effect on FDG uptake. Linear and quadratic developmental trajectories were observed on absolute and relative SUVs, respectively. An increase from posterior-to-anterior and superior-to-inferior pattern was observed in both absolute SUV increase rate and relative SUV peak age. The SUV of each structure was modeled with respect to age, and these models can serve as baselines for the quantitative analysis of cerebral FDG-PET images of children.

The impact of systemic chemotherapy on testicular FDG activity in young men with Hodgkin’s lymphoma

Based on prior reports suggesting a positive correlation between fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/CT and total sperm count and concentration, we sought to identify changes in testicular FDG uptake over the course of chemotherapy in young men with Hodgkin's lymphoma. Fifty-two patients with a mean age of 24.2 years (range 15.5-44.4) at diagnosis monitored with FDG PET/CT to assess treatment response for Hodgkin's lymphoma were selected for this retrospective analysis under an Institutional Review Board waiver. Of the patients, 26 were treated with a chemotherapy regimen known to cause prolonged and sometimes permanent azoospermia (BEACOPP--bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) and 26 with a regimen known to have a much milder effect on gonadal function (ABVD--doxorubicin, bleomycin, vincristine, and dacarbazine). Each patient underwent one FDG PET/CT before treatment and at least one FDG PET/CT after start of chemotherapy. In all examinations, FDG activity was measured in the testes with different quantification metrics: maximum standardized uptake value (SUVmax), SUVmean, functional volume (FV) and total testicular glycolysis (TTG), and blood pool activity determined (SUVmean). Testicular FDG uptake (SUVmax) was significantly associated with blood pool activity (p < 0.001). Furthermore, testicular FDG uptake metrics incorporating volume (e.g., FV and TTG) were associated with age. There was no significant change in SUVmax, SUVmean, FV, and TTG from the PET/CT at baseline to the PET/CTs over the course of chemotherapy either for patients treated with BEACOPP or for patients treated with ABVD. For patients undergoing chemotherapy for Hodgkin's lymphoma, there is a significant association between testicular FDG uptake and blood pool activity, but no significant changes in FDG uptake over the course of chemotherapy. Therefore, FDG uptake may not be a feasible surrogate marker for fertility monitoring in patients with Hodgkin's lymphoma undergoing chemotherapy.

Vascular imaging with positron emission tomography

Atherosclerosis is an inflammatory disease that causes most myocardial infarctions, strokes and acute coronary syndromes. Despite the identification of multiple risk factors and widespread use of drug therapies, it still remains a global health concern with associated costs. Although angiography is established as the gold standard means of detecting coronary artery stenosis, it does not image the vessel wall itself, reporting only on its consequences such as luminal narrowing and obstruction. MRI and computed tomography provide more information about the plaque structure, but recently positron emission tomography (PET) imaging using [(18) F]-fluorodeoxyglucose (FDG) has been advocated as a means of measuring arterial inflammation. This results from the ability of FDG-PET to highlight areas of high glucose metabolism, a feature of macrophages within atherosclerosis, particularly in high-risk plaques. It is suggested that the degree of FDG accumulation in the vessel wall reflects underlying inflammation levels and that tracking any changes in FDG uptake over time or with drug therapy might be a way of getting an early efficacy readout for novel anti-atherosclerotic drugs. Early reports also demonstrate that FDG uptake is correlated with the number of cardiovascular risk factors and possibly even the risk of future cardiovascular events. This review will outline the evidence base, shortcomings and emerging applications for FDG-PET in vascular imaging. Alternative PET tracers and other candidate imaging modalities for measuring vascular inflammation will also be discussed.

North Central Cancer Treatment Group Phase I Trial N057K of Everolimus (RAD001) and Temozolomide in Combination With Radiation Therapy in Patients With Newly Diagnosed Glioblastoma Multiforme

The mammalian target of rapamycin (mTOR) functions within the PI3K/Akt signaling pathway as a critical modulator of cell survival. On the basis of promising preclinical data, the safety and tolerability of therapy with the mTOR inhibitor RAD001 in combination with radiation (RT) and temozolomide (TMZ) was evaluated in this Phase I study. All patients received weekly oral RAD001 in combination with standard chemoradiotherapy, followed by RAD001 in combination with standard adjuvant temozolomide. RAD001 was dose escalated in cohorts of 6 patients. Dose-limiting toxicities were defined during RAD001 combination therapy with TMZ/RT. Eighteen patients were enrolled, with a median follow-up of 8.4 months. Combined therapy was well tolerated at all dose levels, with 1 patient on each dose level experiencing a dose-limiting toxicity: Grade 3 fatigue, Grade 4 hematologic toxicity, and Grade 4 liver dysfunction. Throughout therapy, there were no Grade 5 events, 3 patients experienced Grade 4 toxicities, and 6 patients had Grade 3 toxicities attributable to treatment. On the basis of these results, the recommended Phase II dosage currently being tested is RAD001 70 mg/week in combination with standard chemoradiotherapy. Fluorodeoxyglucose (FDG) positron emission tomography scans also were obtained at baseline and after the second RAD001 dose before the initiation of TMZ/RT; the change in FDG uptake between scans was calculated for each patient. Fourteen patients had stable metabolic disease, and 4 patients had a partial metabolic response. RAD001 in combination with RT/TMZ and adjuvant TMZ was reasonably well tolerated. Changes in tumor metabolism can be detected by FDG positron emission tomography in a subset of patients within days of initiating RAD001 therapy.

Does Computed Tomography or Positron Emission Tomography Response After Neoadjuvant Chemotherapy for Resectable Non–Small-Cell Lung Cancer Predict Survival?

Over the last several decades, measuring tumors on sequential imaging studies has played an essential role in managing patients with lung cancer. Using standardized Response Evaluation Criteria in Solid Tumors (RECIST) at designated time points, patients are stratified into a response category based on the percent change in tumor size. The RECIST guidelines represent an objective assessment of disease, are used to determine duration and reinstitution of therapy, and are ultimately intended as a surrogate marker to predict outcome. Interestingly, this paradigm has been propagated for decades without clear data to support that change in tumor size on radiologic studies will accurately reflect survival. The limitations in stratification by imaging criteria can probably be attributed to the arbitrary selection of percent change used to determine response categories and, more importantly, to the paucity of biologic information in an anatomic abnormality described on a radiographic study. Lung tumors are heterogeneous, and the host response is variable; often a robust inflammatory response to the tumor itself may produce the majority of the radiographic abnormality. Thus, although many investigators have suggested that more accurate tumor measurements, including three-dimensional volumetrics and better resolution, are needed to improve patient stratification, these technical features do not address the fundamental issue of the tumor’s biologic behavior. In the current issue, Tanvetyanon et al report an intriguing prospective trial that examined the ability of changes in computed tomography (CT) or [F]fluorodeoxyglucose (FDG) positron emission tomography (PET) before and after neoadjuvant chemotherapy for resectable non–small-cell lung cancer (NSCLC) to predict survival. This analysis was performed to help define an appropriate imaging evaluation for these patients so that therapy, and hopefully outcome, could be optimized. After thorough analysis, they found that the CT response as measured by the RECIST criteria seems to predict outcomes only in resectable stage III patients. They did not find a statistically significant correlation between the CT response and survival in resectable stage I and II disease. More interestingly, the investigators studied whether FDG-PET was a better predictor of survival compared with conventional imaging. No matter how the data were analyzed, the investigators could not find changes in FDG uptake that predicted outcome. Serial PET studies did not provide the requisite information needed to guide patient management. Although the numbers of patients in this study are relatively small, the conclusions are clear—change in tumor size on CT after neoadjuvant therapy for early-stage resectable NSCLC patients and change in FDG uptake after neoadjuvant therapy for all resectable NSCLC patients did not predict survival. This is a complex conclusion that begs the questions of how to best approach these patients if treatment is to be optimized and why this traditional, seemingly logical measurement strategy is ineffective. The fundamental concept that a tumor cell response equals tumor size response needs to be reconsidered. In some cases, therapy may destroy only the most susceptible tumor cells, leaving the more virulent resistant tumor cells to proliferate. In addition, if there is an increase in the inflammatory reaction, the lesion size could remain stable or even increase. In other cases, the tumor size could potentially decrease, but this may be a result of a reduction in the host inflammatory response, and tumor cells would remain or even propagate. It has been reported that survival correlates with tumor cell viability after therapy and not necessarily with the radiographic response. Despite these limitations, there is currently no alternative approach to response evaluation, and patients are still observed with serial imaging. It would be much more advantageous to work toward a system that predicts, at the time of diagnosis, the most favorable therapeutic plan. Unfortunately, although this is a laudatory goal, attempts to develop personalized medicine and targeted therapy have not yet proved sufficient to enter standard clinical practice. Thus, there remains an unmet need to develop better diagnostic tools. When FDG-PET was introduced into the imaging armamentarium, it was a new direction for radiology that extended beyond traditional anatomic and morphologic information. PET has proved to be useful in some scenarios in the thorax, including differentiating benign from malignant nodules and staging patients with lung cancer. However, the exact mechanism of FDG uptake and distribution within the various cells in a tumor remains unclear. Studies have shown no significant correlation between FDG activity in lung tumors and glucose transporters. Only through a better understanding of the molecular mechanisms that are responsible for radiotracer uptake JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 26 NUMBER 28 OCTOBER 1 2008

PET/CT and hepatic radiation injury in esophageal cancer patients

This paper evaluates the imaging appearance of radiation injury in the liver on positron emission tomography (PET)/computed tomography (CT) in patients with distal esophageal cancer who underwent pre-operative chemoradiation therapy. Twenty-six patients with distal esophageal cancer who received chemoradiotherapy before esophagectomy were included. All patients had baseline and follow-up PET/CT. Fluorodeoxyglucose (FDG) uptake in both left and right lobes of the liver was evaluated. CT findings suggesting radiation damage were documented. Abnormal FDG uptake in the liver was observed in 5 (19%) patients after therapy. These abnormalities were in the left lobe (12%) and right lobe (12%) of the liver. In the irradiated left lobe, FDG uptake increased focally greater than 50% over baseline in two patients (54% and 133%); in one of these patients, biopsy confirmed radiation injury. In the non-irradiated right lobe, standard uptake values (SUV) increased diffusely in two different patients. In one patient, SUV decreased by at least 50% in both the right and left lobes. In the remaining patients, there were no significant changes in FDG uptake. Atrophy and attenuation changes of irradiated liver on CT were found in 15 (58%) patients. In patients receiving chemoradiotherapy, PET/CT may identify metabolic abnormalities in irradiated liver. Such abnormalities should be correlated with other imaging, clinical and laboratory findings to avoid confusion with hepatic metastases.

An In vivo Tumor Model Exploiting Metabolic Response as a Biomarker for Targeted Drug Development

In vivo models that recapitulate oncogene-dependent tumorigenesis will greatly facilitate development of molecularly targeted anticancer therapies. We have developed a model based on activating mutations in c-KIT in gastrointestinal stromal tumors (GISTs). This model comprises murine tumors of FDC-P1 cell lines expressing c-KIT mutations that render the tumors either responsive (V560G) or resistant (D816V) to the small-molecule c-KIT inhibitor, imatinib. Clinically, GIST response to imatinib is associated with rapid reduction in fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET), preceding changes in conventional response criteria by several weeks. Using the FDC-P1 model in small animal PET, FDG uptake into tumors expressing the c-KIT V560G mutation was significantly reduced as early as 4 hours after imatinib treatment. In contrast, no change in FDG uptake was observed in resistant c-KIT D816V-expressing tumors after 48 hours of imatinib treatment. Consistent with the PET results, expression of the glucose transporter, GLUT1, was significantly reduced in V560G tumors at 4 hours, preceding changes in markers of proliferation by several hours. In vitro, imatinib treatment of V560G cells resulted in a reduction of glucose transporter numbers at the cell surface and decreased glucose uptake well before changes in cell viability. Notably, decreased ambient glucose concentrations enhanced the cytotoxic effect of imatinib. Taken together, these data account for the rapidity and significance of the PET response to imatinib and suggest that metabolic effects may contribute to imatinib cytotoxicity. Further, the FDC-P1 model represents a very useful paradigm for molecularly targeted drug development.

Age-associated changes of cerebral glucose metabolic activity in both male and female deaf children: parametric analysis using objective volume of interest and voxel-based mapping

Quantitative analysis of brain activity in the brains of children requires the establishment of age-associated norms. We investigated regional differences in age-associated changes in fluorodeoxyglucose (FDG) uptake in the developmental brains. From 87 (44 male and 43 female) deaf children from the age of 1 to 15, brain FDG positron emission tomography (PET) images were examined after spatial normalization, smoothing, and global normalization to identify brain regions showing a correlation between FDG uptake and age. Using population-based probabilistic volume of interests (VOIs), an objective VOI analysis was performed where normalized relative FDG uptake was measured and their correlations with age were examined in both genders. For the voxel-based analyses, the correlations with age were examined in a general linear model using statistical parametric mapping (SPM99). Both methods revealed that FDG uptake linearly increases with age both in the bilateral inferior prefrontal/orbitofrontal gyri and the right dorsomedial frontal gyrus and decreases in the inferior temporal gyrus and internal capsule white matter. Male children showed age-associated increases of FDG uptake in the right dorsomedial frontal gyrus, and female children in the left dorsolateral prefrontal cortex and thalamus. These changes in FDG uptake in various brain regions may suggest changes in synaptic density or regional activity resulting from normal maturation or deaf-induced adaptation. Caution should be exercised in interpreting the differences in the brain of child patients when compared with adult control's or with a different gender. Further research will be needed to examine if gender difference is manifested in the development rate of behavioral/cognitive functions in association with the age-associated changes of the right medial frontal (male) or the left dorsolateral prefrontal cortices.

Monitoring of Tumour Glucose Metabolism by PET in a Phase I Study Evaluating Hormonal Therapy in Advanced Pancreatic Cancer

Background: Positron emission tomography (PET) determines therapy-induced changes in tumour glucose utilization. Experimental data indicate that cholecystokinin (CCK) stimulates pancreatic cancer growth. In this study in patients with advanced pancreatic cancer, we evaluated the use of fluorodeoxyglucose (FDG) PET compared with magnetic resonance imaging (MRI) in monitoring hormonal therapy using a highly selective, non-peptide CCK receptor antagonist (SR 27897B). Methods: Nineteen patients were enrolled on a 28-day course of SR 27897B. Initially, 4 patients received 20 mg of SR 27897B; 9 patients received 40 mg; and 6 patients 80 mg. Imaging studies, including FDG-PET and MRI, were performed at baseline and on days 14 and 28. Results: No significant changes in FDG uptake by the primary tumours were observed. Rate of progression of disease was 11 (61%) of 18 evaluable patients by MRI. Median survival of all patients enrolled was 2.7 months. SR 27897B was fairly well tolerated at all doses tested. The most common side effects were gastrointestinal disorders such as diarrhoea, flatulence and nausea. Conclusion: SR 27897B, when used alone at the limited doses employed, led neither to an impairment of tumour glucose metabolism nor to a reduction of tumour size in advanced pancreatic cancer.