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Altered cerebral blood flow one month after systemic chemotherapy for breast cancer: a prospective study using pulsed arterial spin labeling MRI perfusion.

Nudelman KN, Wang Y, McDonald BC, Conroy SK, Smith DJ, West JD, O'Neill DP, Schneider BP, Saykin AJ - PLoS ONE (2014)

Bottom Line: These findings indicate that chemotherapy is associated with alterations in cerebral perfusion which are both related to and independent of gray matter changes.This pattern of results suggests the involvement of multiple mechanisms of chemotherapy-induced cognitive dysfunction.Future research is needed to clarify these mechanisms, identify individual differences in susceptibility to treatment-associated changes, and further examine perfusion change over time in survivors.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Training in Research for Behavioral Oncology and Cancer Control Program, Indiana University School of Nursing, Indianapolis, Indiana, United States of America; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.

ABSTRACT
Cerebral structural and functional alterations have been reported after chemotherapy for non-CNS cancers, yet the causative mechanism behind these changes remains unclear. This study employed a novel, non-invasive, MRI-based neuroimaging measure to provide the first direct longitudinal measurement of resting cerebral perfusion in breast cancer patients, which was tested for association with changes in cognitive function and gray matter density. Perfusion was measured using pulsed arterial spin labeling MRI in women with breast cancer treated with (N = 27) or without (N = 26) chemotherapy and matched healthy controls (N = 26) after surgery before other treatments (baseline), and one month after chemotherapy completion or yoked intervals. Voxel-based analysis was employed to assess perfusion in gray matter; changes were examined in relation to overall neuropsychological test performance and frontal gray matter density changes measured by structural MRI. Baseline perfusion was not significantly different across groups. Unlike control groups, chemotherapy-treated patients demonstrated significantly increased perfusion post-treatment relative to baseline, which was statistically significant relative to controls in the right precentral gyrus. This perfusion increase was negatively correlated with baseline overall neuropsychological performance, but was not associated with frontal gray matter density reduction. However, decreased frontal gray matter density was associated with decreased perfusion in bilateral frontal and parietal lobes in the chemotherapy-treated group. These findings indicate that chemotherapy is associated with alterations in cerebral perfusion which are both related to and independent of gray matter changes. This pattern of results suggests the involvement of multiple mechanisms of chemotherapy-induced cognitive dysfunction. Additionally, lower baseline cognitive function may be a risk factor for treatment-associated perfusion dysregulation. Future research is needed to clarify these mechanisms, identify individual differences in susceptibility to treatment-associated changes, and further examine perfusion change over time in survivors.

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Ctx+ perfusion increase compared to HC.Surface rendering of Ctx+ increase compared to HC over time indicates statistically significant perfusion increase in Ctx+ in the right precentral gyrus post-treatment.
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pone-0096713-g004: Ctx+ perfusion increase compared to HC.Surface rendering of Ctx+ increase compared to HC over time indicates statistically significant perfusion increase in Ctx+ in the right precentral gyrus post-treatment.

Mentions: To further elucidate group differences in change over time, each group was tested individually. Only the Ctx+ group had statistically significant perfusion change, demonstrating an increase in perfusion from baseline to one month post-treatment, primarily in superior and posterior brain regions (Figure 3, Table 3). To determine how much of this increase was statistically significantly different than controls, we analyzed group-by-time interactions; results indicated that the Ctx+ group perfusion increased relative to HC specifically in the right precentral gyrus after treatment, indicating that these patients had resting state hyperperfusion discernible by MRI compared to controls (Figure 4, Table 4). Table 6 lists mean perfusion for both time points as well as perfusion change for the right precentral gyrus cluster.


Altered cerebral blood flow one month after systemic chemotherapy for breast cancer: a prospective study using pulsed arterial spin labeling MRI perfusion.

Nudelman KN, Wang Y, McDonald BC, Conroy SK, Smith DJ, West JD, O'Neill DP, Schneider BP, Saykin AJ - PLoS ONE (2014)

Ctx+ perfusion increase compared to HC.Surface rendering of Ctx+ increase compared to HC over time indicates statistically significant perfusion increase in Ctx+ in the right precentral gyrus post-treatment.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016018&req=5

pone-0096713-g004: Ctx+ perfusion increase compared to HC.Surface rendering of Ctx+ increase compared to HC over time indicates statistically significant perfusion increase in Ctx+ in the right precentral gyrus post-treatment.
Mentions: To further elucidate group differences in change over time, each group was tested individually. Only the Ctx+ group had statistically significant perfusion change, demonstrating an increase in perfusion from baseline to one month post-treatment, primarily in superior and posterior brain regions (Figure 3, Table 3). To determine how much of this increase was statistically significantly different than controls, we analyzed group-by-time interactions; results indicated that the Ctx+ group perfusion increased relative to HC specifically in the right precentral gyrus after treatment, indicating that these patients had resting state hyperperfusion discernible by MRI compared to controls (Figure 4, Table 4). Table 6 lists mean perfusion for both time points as well as perfusion change for the right precentral gyrus cluster.

Bottom Line: These findings indicate that chemotherapy is associated with alterations in cerebral perfusion which are both related to and independent of gray matter changes.This pattern of results suggests the involvement of multiple mechanisms of chemotherapy-induced cognitive dysfunction.Future research is needed to clarify these mechanisms, identify individual differences in susceptibility to treatment-associated changes, and further examine perfusion change over time in survivors.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Training in Research for Behavioral Oncology and Cancer Control Program, Indiana University School of Nursing, Indianapolis, Indiana, United States of America; Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.

ABSTRACT
Cerebral structural and functional alterations have been reported after chemotherapy for non-CNS cancers, yet the causative mechanism behind these changes remains unclear. This study employed a novel, non-invasive, MRI-based neuroimaging measure to provide the first direct longitudinal measurement of resting cerebral perfusion in breast cancer patients, which was tested for association with changes in cognitive function and gray matter density. Perfusion was measured using pulsed arterial spin labeling MRI in women with breast cancer treated with (N = 27) or without (N = 26) chemotherapy and matched healthy controls (N = 26) after surgery before other treatments (baseline), and one month after chemotherapy completion or yoked intervals. Voxel-based analysis was employed to assess perfusion in gray matter; changes were examined in relation to overall neuropsychological test performance and frontal gray matter density changes measured by structural MRI. Baseline perfusion was not significantly different across groups. Unlike control groups, chemotherapy-treated patients demonstrated significantly increased perfusion post-treatment relative to baseline, which was statistically significant relative to controls in the right precentral gyrus. This perfusion increase was negatively correlated with baseline overall neuropsychological performance, but was not associated with frontal gray matter density reduction. However, decreased frontal gray matter density was associated with decreased perfusion in bilateral frontal and parietal lobes in the chemotherapy-treated group. These findings indicate that chemotherapy is associated with alterations in cerebral perfusion which are both related to and independent of gray matter changes. This pattern of results suggests the involvement of multiple mechanisms of chemotherapy-induced cognitive dysfunction. Additionally, lower baseline cognitive function may be a risk factor for treatment-associated perfusion dysregulation. Future research is needed to clarify these mechanisms, identify individual differences in susceptibility to treatment-associated changes, and further examine perfusion change over time in survivors.

Show MeSH
Related in: MedlinePlus