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Microstructural white matter alterations associated to neurocognitive deficits in childhood leukemia survivors treated with cranial radiotherapy–a diffusional kurtosis study

Follin, Cecilia LU ; Svärd, Daniel LU ; van Westen, Danielle LU orcid ; Björkman-Burtscher, Isabella M. LU ; Sundgren, Pia C. LU orcid ; Fjalldal, Sigridur LU ; Lätt, Jimmy LU ; Nilsson, Markus LU ; Johanson, Aki LU and Erfurth, Eva Marie LU (2019) In Acta Oncologica 58(7). p.1021-1028
Abstract

Background: Cranial radiotherapy (CRT) is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Diffusion tensor imaging (DTI) and diffusional kurtosis imaging (DKI) are MRI techniques that quantify microstructural changes in brain white matter (WM) and DKI is regarded as the more sensitive of them. Our aim was to more thoroughly understand the nature of cognitive deficits after cranial radiotherapy (CRT) in adulthood after childhood ALL. Material and methods: Thirty-eight (21 women) ALL survivors, median age 38 (27–46) years, were investigated at median 34 years after diagnosis. All had been treated with a CRT dose of 24 Gy and with 11 years of complete hormone supplementation.... (More)

Background: Cranial radiotherapy (CRT) is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Diffusion tensor imaging (DTI) and diffusional kurtosis imaging (DKI) are MRI techniques that quantify microstructural changes in brain white matter (WM) and DKI is regarded as the more sensitive of them. Our aim was to more thoroughly understand the nature of cognitive deficits after cranial radiotherapy (CRT) in adulthood after childhood ALL. Material and methods: Thirty-eight (21 women) ALL survivors, median age 38 (27–46) years, were investigated at median 34 years after diagnosis. All had been treated with a CRT dose of 24 Gy and with 11 years of complete hormone supplementation. DTI and DKI parameters were determined and neurocognitive tests were performed in ALL survivors and 29 matched controls. Results: ALL survivors scored lower than controls in neurocognitive tests of vocabulary, memory, learning capacity, spatial ability, executive functions, and attention (p <.001). The survivors had altered DTI parameters in the fornix, uncinate fasciculus, and ventral cingulum (all p <.05) and altered DKI parameters in the fornix, uncinate fasciculus, and dorsal and ventral cingulum (p <.05). Altered DTI parameters in the fornix were associated with impaired episodic verbal memory (r = −0.40, p <.04). The left and right uncinate fasciculus (r = 0.6, p <.001), (r = −0.5, p <.02) as well as the right ventral cingulum (r = 0.5, p <.007) were associated with impaired episodic visual memory. Altered DKI parameters in the fornix, right uncinate fasciculus (r = 0.3, r = 0.05, p =.02), and ventral cingulum (r = 0.3, p =.02) were associated with impaired results of episodic visual memory. Conclusion: ALL survivors with cognitive deficits demonstrated microstructural damage in several WM tracts that were more extensive with DKI as compared to DTI; this might be a marker of radiation and chemotherapy neurotoxicity underlying cognitive dysfunction.

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; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Acta Oncologica
volume
58
issue
7
pages
1021 - 1028
publisher
Taylor & Francis
external identifiers
  • scopus:85061447988
  • pmid:30747019
ISSN
0284-186X
DOI
10.1080/0284186X.2019.1571279
language
English
LU publication?
yes
id
44322a77-cc6f-4baf-a8ee-cc9b53698014
date added to LUP
2019-02-21 14:07:05
date last changed
2024-04-01 22:21:52
@article{44322a77-cc6f-4baf-a8ee-cc9b53698014,
  abstract     = {{<p>Background: Cranial radiotherapy (CRT) is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Diffusion tensor imaging (DTI) and diffusional kurtosis imaging (DKI) are MRI techniques that quantify microstructural changes in brain white matter (WM) and DKI is regarded as the more sensitive of them. Our aim was to more thoroughly understand the nature of cognitive deficits after cranial radiotherapy (CRT) in adulthood after childhood ALL. Material and methods: Thirty-eight (21 women) ALL survivors, median age 38 (27–46) years, were investigated at median 34 years after diagnosis. All had been treated with a CRT dose of 24 Gy and with 11 years of complete hormone supplementation. DTI and DKI parameters were determined and neurocognitive tests were performed in ALL survivors and 29 matched controls. Results: ALL survivors scored lower than controls in neurocognitive tests of vocabulary, memory, learning capacity, spatial ability, executive functions, and attention (p &lt;.001). The survivors had altered DTI parameters in the fornix, uncinate fasciculus, and ventral cingulum (all p &lt;.05) and altered DKI parameters in the fornix, uncinate fasciculus, and dorsal and ventral cingulum (p &lt;.05). Altered DTI parameters in the fornix were associated with impaired episodic verbal memory (r = −0.40, p &lt;.04). The left and right uncinate fasciculus (r = 0.6, p &lt;.001), (r = −0.5, p &lt;.02) as well as the right ventral cingulum (r = 0.5, p &lt;.007) were associated with impaired episodic visual memory. Altered DKI parameters in the fornix, right uncinate fasciculus (r = 0.3, r = 0.05, p =.02), and ventral cingulum (r = 0.3, p =.02) were associated with impaired results of episodic visual memory. Conclusion: ALL survivors with cognitive deficits demonstrated microstructural damage in several WM tracts that were more extensive with DKI as compared to DTI; this might be a marker of radiation and chemotherapy neurotoxicity underlying cognitive dysfunction.</p>}},
  author       = {{Follin, Cecilia and Svärd, Daniel and van Westen, Danielle and Björkman-Burtscher, Isabella M. and Sundgren, Pia C. and Fjalldal, Sigridur and Lätt, Jimmy and Nilsson, Markus and Johanson, Aki and Erfurth, Eva Marie}},
  issn         = {{0284-186X}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{7}},
  pages        = {{1021--1028}},
  publisher    = {{Taylor & Francis}},
  series       = {{Acta Oncologica}},
  title        = {{Microstructural white matter alterations associated to neurocognitive deficits in childhood leukemia survivors treated with cranial radiotherapy–a diffusional kurtosis study}},
  url          = {{http://dx.doi.org/10.1080/0284186X.2019.1571279}},
  doi          = {{10.1080/0284186X.2019.1571279}},
  volume       = {{58}},
  year         = {{2019}},
}