Time-course of effects of external beam radiation on [18F]FDG uptake in healthy tissue and bone marrow.

The utility of PET for monitoring responses to radiation therapy have been complicated by metabolically active processes in surrounding normal tissues. We examined the time-course of [18F]FDG uptake in normal tissues using small animal-dedicated PET during the 2 month period following external beam radiation. Four mice received 12 Gy of external beam radiation, in a single fraction to the left half of the body. Small animal [18F]FDG-PET scans were acquired for each mouse at 0 (pre-radiation), 1, 2, 3, 4, 5, 8, 12, 19, 24, and 38 days following irradiation. [18F]FDG activity in various tissues was compared between irradiated and non-irradiated body halves before, and at each time point after irradiation. Radiation had a significant impact on [18F]FDG uptake in previously healthy tissues, and time-course of effects differed in different types of tissues. For example, liver tissue demonstrated increased uptake, particularly over days 3-12, with the mean left to right uptake ratio increasing 52% over mean baseline values (p < 0.0001). In contrast, femoral bone marrow uptake demonstrated decreased uptake, particularly over days 2-8, with the mean left to right uptake ratio decreasing 26% below mean baseline values (p = 0.0005). Significant effects were also seen in lung and brain tissue. Radiation had diverse effects on [18F]FDG uptake in previously healthy tissues. These kinds of data may help lay groundwork for a systematically acquired database of the time-course of effects of radiation on healthy tissues, useful for animal models of cancer therapy imminently, as well as interspecies extrapolations pertinent to clinical application eventually

Brain Metabolism During A Lower Extremity Voluntary Movement Task in Children With Spastic Cerebral Palsy.

Reduced selective voluntary motor control (SVMC) is a primary impairment due to corticospinal tract (CST) injury in spastic cerebral palsy (CP). There are few studies of brain metabolism in CP and none have examined brain metabolism during a motor task. Nine children with bilateral spastic CP [Age: 6-11 years, Gross Motor Function Classification System (GMFCS) Levels II-V] completed this study. SVMC was evaluated using Selective Control Assessment of the Lower Extremity (SCALE) ranging from 0 (absent) to 10 (normal). Brain metabolism was measured using positron emission tomography (PET) scanning in association with a selective ankle motor task. Whole brain activation maps as well as ROI averaged metabolic activity were correlated with SCALE scores. The contralateral sensorimotor and superior parietal cortex were positively correlated with SCALE scores (p < 0.0005). In contrast, a negative correlation of metabolic activity with SCALE was found in the cerebellum (p < 0.0005). Subsequent ROI analysis showed that both ipsilateral and contralateral cerebellar metabolism correlated with SCALE but the relationship for the ipsilateral cerebellum was stronger (R 2 = 0.80, p < 0.001 vs. R 2 = 0.46, p = 0.045). Decreased cortical and increased cerebellar activation in children with less SVMC may be related to task difficulty, activation of new motor learning paradigms in the cerebellum and potential engagement of alternative motor systems when CSTs are focally damaged. These results support SCALE as a clinical correlate of neurological impairment

Time-course of effects of external beam radiation on [18F]FDG uptake in healthy tissue and bone marrow.

The utility of PET for monitoring responses to radiation therapy have been complicated by metabolically active processes in surrounding normal tissues. We examined the time-course of [18F]FDG uptake in normal tissues using small animal-dedicated PET during the 2 month period following external beam radiation. Four mice received 12 Gy of external beam radiation, in a single fraction to the left half of the body. Small animal [18F]FDG-PET scans were acquired for each mouse at 0 (pre-radiation), 1, 2, 3, 4, 5, 8, 12, 19, 24, and 38 days following irradiation. [18F]FDG activity in various tissues was compared between irradiated and non-irradiated body halves before, and at each time point after irradiation. Radiation had a significant impact on [18F]FDG uptake in previously healthy tissues, and time-course of effects differed in different types of tissues. For example, liver tissue demonstrated increased uptake, particularly over days 3-12, with the mean left to right uptake ratio increasing 52% over mean baseline values (p < 0.0001). In contrast, femoral bone marrow uptake demonstrated decreased uptake, particularly over days 2-8, with the mean left to right uptake ratio decreasing 26% below mean baseline values (p = 0.0005). Significant effects were also seen in lung and brain tissue. Radiation had diverse effects on [18F]FDG uptake in previously healthy tissues. These kinds of data may help lay groundwork for a systematically acquired database of the time-course of effects of radiation on healthy tissues, useful for animal models of cancer therapy imminently, as well as interspecies extrapolations pertinent to clinical application eventually

Cognitive function after the initiation of adjuvant endocrine therapy in early-stage breast cancer: an observational cohort study.

PurposeThis report examines cognitive complaints and neuropsychological (NP) testing outcomes in patients with early-stage breast cancer after the initiation of endocrine therapy (ET) to determine whether this therapy plays any role in post-treatment cognitive complaints.Patients and methodsOne hundred seventy-three participants from the Mind Body Study (MBS) observational cohort provided data from self-report questionnaires and NP testing obtained at enrollment (T1, before initiation of ET), and 6 months later (T2). Bivariate analyses compared demographic and treatment variables, cognitive complaints, depressive symptoms, quality of life, and NP functioning between those who received ET versus not. Multivariable linear regression models examined predictors of cognitive complaints at T2, including selected demographic variables, depressive symptoms, ET use, and other medical variables, along with NP domains that were identified in bivariate analyses.ResultsSeventy percent of the 173 MBS participants initiated ET, evenly distributed between tamoxifen or aromatase inhibitors. ET-treated participants reported significantly increased language and communication (LC) cognitive complaints at T2 (P = .003), but no significant differences in NP test performance. Multivariable regression on LC at T2 found higher LC complaints significantly associated with T1 LC score (P < .001), ET at T2 (P = .004), interaction between ET and past hormone therapy (HT) (P < .001), and diminished improvement in NP psychomotor function (P = .05). Depressive symptoms were not significant (P = .10).ConclusionHigher LC complaints are significantly associated with ET 6 months after starting treatment and reflect diminished improvements in some NP tests. Past HT is a significant predictor of higher LC complaints after initiation of ET

Cognitive function after the initiation of adjuvant endocrine therapy in early-stage breast cancer: an observational cohort study.

PurposeThis report examines cognitive complaints and neuropsychological (NP) testing outcomes in patients with early-stage breast cancer after the initiation of endocrine therapy (ET) to determine whether this therapy plays any role in post-treatment cognitive complaints.Patients and methodsOne hundred seventy-three participants from the Mind Body Study (MBS) observational cohort provided data from self-report questionnaires and NP testing obtained at enrollment (T1, before initiation of ET), and 6 months later (T2). Bivariate analyses compared demographic and treatment variables, cognitive complaints, depressive symptoms, quality of life, and NP functioning between those who received ET versus not. Multivariable linear regression models examined predictors of cognitive complaints at T2, including selected demographic variables, depressive symptoms, ET use, and other medical variables, along with NP domains that were identified in bivariate analyses.ResultsSeventy percent of the 173 MBS participants initiated ET, evenly distributed between tamoxifen or aromatase inhibitors. ET-treated participants reported significantly increased language and communication (LC) cognitive complaints at T2 (P = .003), but no significant differences in NP test performance. Multivariable regression on LC at T2 found higher LC complaints significantly associated with T1 LC score (P < .001), ET at T2 (P = .004), interaction between ET and past hormone therapy (HT) (P < .001), and diminished improvement in NP psychomotor function (P = .05). Depressive symptoms were not significant (P = .10).ConclusionHigher LC complaints are significantly associated with ET 6 months after starting treatment and reflect diminished improvements in some NP tests. Past HT is a significant predictor of higher LC complaints after initiation of ET