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Apparent diffusion coefficient values effectively predict cell proliferation and determine oligodendroglioma grade

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Xiaoai Ke
Xiaoai Ke
Xiaoai Ke
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Jun Zhao
Jun Zhao
Jun Zhao
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Xianwang Liu
Xianwang Liu
Xianwang Liu
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Qing Zhou
Qing Zhou
Qing Zhou
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Abstract and Figures

This study aims to evaluate the value of conventional magnetic resonance imaging (MRI) features and apparent diffusion coefficient (ADC) values in differentiating oligodendroglioma of various grades and explore the correlation between ADC and Ki-67. The preoperative MRI data of 99 patients with World Health Organization (WHO) grades 2 (n = 42) and 3 (n = 57) oligodendroglioma confirmed by surgery and pathology were retrospectively analyzed. Conventional MRI features, ADCmean, ADCmin, and normalized ADC (nADC) were compared between the two groups. A receiver operating characteristic curve was used to evaluate each parameter’s diagnostic efficacy in differentiating the two tumor types. Each tumor’s Ki-67 proliferation index was also measured to explore its relationship with the ADC value. Compared with WHO2 grade tumors, WHO3 grade tumors had a larger maximum diameter and more significant cystic degeneration/necrosis, edema, and moderate/severe enhancement (all P < 0.05). The ADCmin, ADCmean, and nADC values of the WHO3 and WHO2 grade tumors were significantly different, and the ADCmin value most accurately distinguished the two tumor types, yielding an area under the curve value of 0.980. When 0.96 × 10⁻³ mm²/s was used as the differential diagnosis threshold, the sensitivity, specificity, and accuracy of the two groups were 100%, 93.00%, and 96.96%, respectively. The ADCmin (r = –0.596), ADCmean (r = − 0.590), nADC (r = − 0.577), and Ki-67 proliferation index values had significantly negative correlations (all P < 0.05). Conventional MRI features and ADC values are beneficial in the noninvasive prediction of the WHO grade and tumor proliferation rate of oligodendroglioma.
Forty-seven-year-old male patient with right temporal lobe WHO2 grade OD (a–f). The irregular lesion in the right temporal lobe with uniform low signal on T1WI and uniform high signal on T2WI, clear tumor brain boundary, no edema around the tumor, and no significant enhancement on contrast-enhanced T1WI images. DWI exhibited a slightly low signal, whereas ADC exhibited a high signal (ADCmean = 1.37 × 10–3 mm.²/s). Histopathological examination revealed the diffuse distribution of tumor cells, consistent cell size and shape, small nucleus, round and oval, deep staining, and rare mitotic image (hematoxylin and eosin-stained sections, × 200)
Forty-seven-year-old male patient with right temporal lobe WHO2 grade OD (a–f). The irregular lesion in the right temporal lobe with uniform low signal on T1WI and uniform high signal on T2WI, clear tumor brain boundary, no edema around the tumor, and no significant enhancement on contrast-enhanced T1WI images. DWI exhibited a slightly low signal, whereas ADC exhibited a high signal (ADCmean = 1.37 × 10–3 mm.²/s). Histopathological examination revealed the diffuse distribution of tumor cells, consistent cell size and shape, small nucleus, round and oval, deep staining, and rare mitotic image (hematoxylin and eosin-stained sections, × 200)
… 
Fifty-three-year-old male patient with left frontal lobe WHO3 grade OD (a–f). The irregular lesion in the left frontal lobe with nonuniform low signal on T1WI and nonuniform high signal on T2WI, with cystic necrosis area, unclear tumor brain boundary, and peritumoral edema, T1 enhancement exhibited obvious, ring-shaped enhancement. The solid component of the tumor exhibited a high signal on DWI and low signal on ADC (ADCmin = 0.73 × 10–3 mm.²/s). Histopathological examination revealed diffuse distribution of tumor cells, obvious abnormity, vascular hyperplasia with endothelial cell proliferation, and tumor cell necrosis in some areas.(hematoxylin and eosin-stained sections, × 200)
Fifty-three-year-old male patient with left frontal lobe WHO3 grade OD (a–f). The irregular lesion in the left frontal lobe with nonuniform low signal on T1WI and nonuniform high signal on T2WI, with cystic necrosis area, unclear tumor brain boundary, and peritumoral edema, T1 enhancement exhibited obvious, ring-shaped enhancement. The solid component of the tumor exhibited a high signal on DWI and low signal on ADC (ADCmin = 0.73 × 10–3 mm.²/s). Histopathological examination revealed diffuse distribution of tumor cells, obvious abnormity, vascular hyperplasia with endothelial cell proliferation, and tumor cell necrosis in some areas.(hematoxylin and eosin-stained sections, × 200)
… 
The use of ADCmean, ADCmin, and nADC values in the differential diagnosis of WHO grades 2 and 3 OD. Their areas under the curve were 0.968 ± 0.018, 0.980 ± 0.015, and 0.973 ± 0.015
The use of ADCmean, ADCmin, and nADC values in the differential diagnosis of WHO grades 2 and 3 OD. Their areas under the curve were 0.968 ± 0.018, 0.980 ± 0.015, and 0.973 ± 0.015
… 
Correlation linear heat map. The ADCmin, ADCmean, and nADC values of OD were all negatively correlated with the Ki-67 proliferation index to varying degrees, and the correlation coefficients (r) were –0.596, –0.590, and –0.577, respectively (a–c)
Correlation linear heat map. The ADCmin, ADCmean, and nADC values of OD were all negatively correlated with the Ki-67 proliferation index to varying degrees, and the correlation coefficients (r) were –0.596, –0.590, and –0.577, respectively (a–c)
… 
Comparison of the Ki-67 proliferation index between WHO grade 2 and 3 ODs
Comparison of the Ki-67 proliferation index between WHO grade 2 and 3 ODs
… 
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Vol.:(0123456789)
1 3
Neurosurgical Review (2023) 46:83
https://doi.org/10.1007/s10143-023-01989-3
RESEARCH
Apparent diffusion coefficient values effectively predict cell
proliferation anddetermine oligodendroglioma grade
XiaoaiKe1,2,3· JunZhao1,2,3,4· XianwangLiu1,2,3,4· QingZhou1,2,3,4· WenCheng1,2,3· PengZhang5· JunlinZhou1,2,3,4
Received: 10 January 2023 / Revised: 27 February 2023 / Accepted: 27 March 2023 / Published online: 6 April 2023
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023
Abstract
This study aims to evaluate the value of conventional magnetic resonance imaging (MRI) features and apparent diffusion
coefficient (ADC) values in differentiating oligodendroglioma of various grades and explore the correlation between ADC
and Ki-67. The preoperative MRI data of 99 patients with World Health Organization (WHO) grades 2 (n = 42) and 3
(n = 57) oligodendroglioma confirmed by surgery and pathology were retrospectively analyzed. Conventional MRI features,
ADCmean, ADCmin, and normalized ADC (nADC) were compared between the two groups. A receiver operating charac-
teristic curve was used to evaluate each parameter’s diagnostic efficacy in differentiating the two tumor types. Each tumor’s
Ki-67 proliferation index was also measured to explore its relationship with the ADC value. Compared with WHO2 grade
tumors, WHO3 grade tumors had a larger maximum diameter and more significant cystic degeneration/necrosis, edema, and
moderate/severe enhancement (all P < 0.05). The ADCmin, ADCmean, and nADC values of the WHO3 and WHO2 grade
tumors were significantly different, and the ADCmin value most accurately distinguished the two tumor types, yielding an
area under the curve value of 0.980. When 0.96 × 10−3 mm2/s was used as the differential diagnosis threshold, the sensitiv-
ity, specificity, and accuracy of the two groups were 100%, 93.00%, and 96.96%, respectively. The ADCmin (r = –0.596),
ADCmean (r = − 0.590), nADC (r = − 0.577), and Ki-67 proliferation index values had significantly negative correlations
(all P < 0.05). Conventional MRI features and ADC values are beneficial in the noninvasive prediction of the WHO grade
and tumor proliferation rate of oligodendroglioma.
Keywords Oligodendroglioma· Ki-67· Proliferation index· Magnetic resonance imaging· Apparent diffusion coefficient
Introduction
Oligodendroglioma (OD) is a rare primary neuroepithe-
lial tumor that originates from neural progenitor cells with
glial precursors [1, 22]. It accounts for approximately 5%
of primary intracranial tumors. The peak age of adult-onset
is 40–60years. The tumors are mainly located in the cor-
tex subcortical area. They diffuse into the adjacent white
matter, predominantly in the frontal lobe [26]. The 2021
World Health Organization classification of tumors of the
central nervous system (WHO-CNS) eliminated the ambigu-
ous entity oligoastrocytoma, based on molecular and histo-
logical changes, and classified it as OD with intratumoral
grading. IDH1 or IDH2 mutation and codeletion of chromo-
some arms 1p and 19q (WHO-CNS grade 2–3) [20]. Previ-
ous studies have revealed differences in treatment methods
and prognosis between WHO grade 2 (OD) and 3 (proto-
anaplastic OD) tumors. The average survival time of patients
with WHO grade 2 tumors is longer than that of those with
Xiaoai Ke and Jun Zhao contributed equally to this study.
* Junlin Zhou
ery_zhoujl@lzu.edu.cn
1 Department ofRadiology, Lanzhou University Second
Hospital, Chengguan District, Cuiyingmen No.82,
Lanzhou730030, Gansu, People’sRepublicofChina
2 Key Laboratory ofMedical Imaging ofGansu Province,
Lanzhou, China
3 Gansu International Scientific andTechnological
Cooperation Base ofMedical Imaging Artificial Intelligence,
Lanzhou, China
4 Second Clinical School, Lanzhou University, Lanzhou, China
5 Department ofPathology, Lanzhou University Second
Hospital, Lanzhou, Gansu, China
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
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BACKGROUND AND PURPOSE For diagnosis of medulloblastoma, the updated World Health Organization classification now demands for genetic typing, defining more precisely the tumor biology, therapy, and prognosis. We investigated potential associations between magnetic resonance imaging (MRI) parameters including apparent diffusion coefficient (ADC) and neuropathologic features of medulloblastoma, focusing on genetic subtypes. METHODS This study was a retrospective single‐center analysis of 32 patients (eight females, median age = 9 years [range, 1‐57], mean 12.6 ± 11.3) from 2012 to 2019. Genetic subtypes (wingless [WNT]; sonic hedgehog [SHH]; non‐WNT/non‐SHH), histopathology, immunohistochemistry (p53, Ki67), and the following MRI parameters were correlated: tumor volume, location (midline, pontocerebellar, and cerebellar hemisphere), edema, hydrocephalus, metastatic disease (presence/absence and each), contrast‐enhancement (minor, moderate, and distinct), cysts (none, small, and large), hemorrhage (none, minor, and major), and ADCmean. The ADCmean was calculated using manually set regions of interest within the solid tumor. Statistics comprised univariate and multivariate testing. RESULTS Out of 32 tumors, three tumors were WNT activated (9.4%), 13 (40.6%) SHH activated, and 16 (50.0%) non‐WNT/non‐SHH. Hemispherical location (n = 7/8, P = .003) and presence of edema (8/8; P < .001, specificity 100%, positive predictive value 100%) were significantly associated with SHH activation. The combined parameter “no edema + no metastatic disease + cysts” significantly discriminated WNT‐activated from SHH‐activated medulloblastoma (P = .036). ADCmean (10–6 mm2/s) was 484 for WNT‐activated, 566 for SHH‐activated, and 624 for non‐WNT/non‐SHH subtypes (P = .080). A significant negative correlation was found between ADCmean and Ki67 (r = –.364, P = .040). CONCLUSION MRI analysis enabled noninvasive differentiation of SHH‐activated medulloblastoma. ADC alone was not reliable for genetic characterization, but associated with tumor proliferation rate.
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Improving the characterization of meningioma microstructure in proton therapy from conventional apparent diffusion coefficient measurements using Monte Carlo simulations of diffusion MRI
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Full-text available
  • Feb 2021
  • MED PHYS
Purpose Proton therapy could benefit from noninvasively gaining tumor microstructure information, at both planning and monitoring stages. The anatomical location of brain tumors, such as meningiomas, often hinders the recovery of such information from histopathology, and conventional noninvasive imaging biomarkers, like the apparent diffusion coefficient (ADC) from diffusion‐weighted MRI (DW‐MRI), are nonspecific. The aim of this study was to retrieve discriminative microstructural markers from conventional ADC for meningiomas treated with proton therapy. These markers were employed for tumor grading and tumor response assessment. Methods DW‐MRIs from patients affected by meningioma and enrolled in proton therapy were collected before (n = 35) and 3 months after (n = 25) treatment. For the latter group, the risk of an adverse outcome was inferred by their clinical history. Using Monte Carlo methods, DW‐MRI signals were simulated from packings of synthetic cells built with well‐defined geometrical and diffusion properties. Patients’ ADC was modeled as a weighted sum of selected simulated signals. The weights that best described a patient’s ADC were determined through an optimization procedure and used to estimate a set of markers of tumor microstructure: diffusion coefficient (D), volume fraction (vf), and radius (R). Apparent cellularity (ρapp) was estimated from vf and R for an easier clinical interpretability. Differences between meningothelial and atypical subtypes, and low‐ and high‐grade meningiomas were assessed with nonparametric statistical tests, whereas sensitivity and specificity with ROC analyses. Similar analyses were performed for patients showing low or high risk of an adverse outcome to preliminary evaluate response to treatment. Results Significant (P < 0.05) differences in median ADC, D, vf, R, and ρapp values were found when comparing meningiomas’ subtypes and grades. ROC analyses showed that estimated microstructural parameters reached higher specificity than ADC for subtyping (0.93 for D and vf vs 0.80 for ADC) and grading (0.75 for R vs 0.67 for ADC). High‐ and low‐risk patients showed significant differences in ADC and microstructural parameters. The skewness of ρapp was the parameter with highest AUC (0.90) and sensitivity (0.75). Conclusions Matching measured with simulated ADC yielded a set of potential imaging markers for meningiomas grading and response monitoring in proton therapy, showing higher specificity than conventional ADC. These markers can provide discriminative information about spatial patterns of tumor microstructure implying important advantages for patient‐specific proton therapy workflows.
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