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Imaging of midline crossing IDH mutant 1p19q co-deleted high-grade oligodendroglioma: role of ASL perfusion and spectroscopy.

Published onApr 15, 2023
Imaging of midline crossing IDH mutant 1p19q co-deleted high-grade oligodendroglioma: role of ASL perfusion and spectroscopy.


A 54-year-old woman returned from hairdressers to a property she used to live 8 years ago. She was convinced that she still lives there. No evidence of meningoencephalitis clinically. GCS was 15 at the time of the first scan. Episodes of memory loss intermittently and personality changes over the preceding 1-2 months.

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Non-contrast CT findings:

Figure 1

Figure 1: Non-contrast CT scan shows mid-line crossing hypo-density with calcification.

Midline crossing hypodensity is noted in the bi-frontal location, with calcified foci in the bilateral frontal cortices.

Differentials on the CT scan include glioblastoma, but calcifications are atypical. Oligodendrogliomas sometimes can cross the midline, but this much invasion is atypical for oligodendrogliomas which are usually low-grade. Lymphomas, when treated especially with radiation, can show calcification, but there was no history of radiation in our patient. MRI with contrast, multi-voxel spectroscopy, and ASL were advised in the multidisciplinary team meeting (MDT).

MRI brain
T2 axial image shows T2 hyperintense midline crossing lesion.
Figure 2

Figure 2: T2 axial image shows a hyperintense midline crossing lesion.

Figure 3

Figure 3: ADC map, b1000 DWI followed by b0 DWI images from left to right. Showing patches of diffusion restriction, especially near the midline where the lesion involves the septum pellucidum.

Figure 4

Figure 4: T1 pre and contrast images from left to right. No evidence of significant enhancement is noted.

Predominantly T2 and FLAIR hyperintense lesion is noted crossing the midline involving the bilateral frontal lobes, genu of the corpus callosum, and the bilateral fornix. There are patchy areas of diffusion restriction. No evidence of necrosis, peripheral diffusion restriction, or peripheral enhancement was noted. The differential in conventional imaging can be low-grade glioma with infiltration, which can be seen in diffuse astrocytomas. IDH wild glioblastoma can also be considered, given the few areas of diffusion restriction and midline crossing characteristics.

Perfusion imaging with ASL (arterial spin labeling)

Figure 5

Figure 5: Arterial spin labeling axial image fused with T1 post-contrast image, showing increased perfusion in the lesion, giving the butterfly-like appearance on perfusion. The perfusion is very high, the quantification ROI in the left lower corner shows an average of 195 ml/100g/min flow in the tumor.

Very high perfusion is noted in the bifrontal midline crossing lesion. The average TBF (tumor blood flow) is 195 ml/100mg/min. This range of increased perfusion is noted in glioblastoma or high-grade astrocytomas [1] [2]. Lymphoma in literature has shown relatively less hyperperfusion compared to glioblastomas and high-grade gliomas [3] [4]. However, there is no literature comparing lymphoma with low-grade glioma. But given the very high perfusion and patchy diffusion restriction, low-grade glioma was not in the differential.

Multivoxel spectroscopy
Figure 6

Figure 6: Multivoxel spectroscopy maps, the voxel in current image is placed in the tumor showing increased Choline and Creatinine peak with low NAA peak. The head maps below shows lipid lactate map, Ch/NAA map and Ch/Cr map from right to left.

Figure 7

Figure 7: Multivoxel spectroscopy myoinositol map on the right side and Choline/NAA map on the left side.

Multivoxel spectroscopy shows increased myoinositol in the spectroscopy maps. Increased myoinositol is associated with gliomas and differentiating features from lymphoma, according to Nagashima et al. [5]. There are increased Choline/NAA and Choline/Creatine ratios in the areas of high perfusion on ASL. Choline/NAA and Choline/Creatine ratios were higher than in low-grade IDH mutant gliomas [6]. We were thinking in line with IDH mutant Grade 4 or IDH wild Grade 4 glioma.

Differential diagnosis

The integrated differential based on imaging was high-grade IDH mutant glioma Grade 4. Another differential was IDH wild glioblastoma Grade 4.

Histopathological / Genetic correlation


The biopsy done first did not reveal good sample tissue, and therefore biopsy was repeated, which was histologically graded as low-grade glioma. Because of the diffuse nature of the tumor, it is possible that the high cellular tissue was missed on the biopsy. Pathology colleagues were advised to run more genetic panels to resolve the radio-pathological discrepancy.

Genetic update

Follow-up genetic update shows the tumor being an IDH mutant 1p19q codeleted and CDKN2A/B homozygously codeleted and therefore was upgraded to a higher grade (grade 3 oligodendroglioma according to WHO-2021 classification). There is no Grade 4 oligodendroglioma according to the WHO-2021 classification.

Prognosis and Post-treatment scan

CDKN 2A/B homozygous codeletion is more important in glioma stratification in IDH mutant tumors, rather more important than conventional grading [7]. Our patient was treated with radical radiotherapy after Grade 3 classification. The post-radiation scan done after six months showed a significant reduction in the lesion size and a significant reduction in the areas showing increased perfusion.

Figure 8

Figure 8: Post-treatment T2 axial. Compared with the pre-treatment scan, there is a significant reduction in the size of the midline crossing tumor.

Figure 9

Figure 9: ASL (arterial spin labeling) image fused with T2 axial. A significant reduction in perfusion was noted in the post-treatment scan.


Genetic subtypes within 1p19q codeleted glioma showing increased perfusion have been described in the literature with the DSC perfusion technique [8] [9]. In our patient, this was noted with the ASL perfusion technique. Choline/Creatine ratios are reported to be higher in high-grade gliomas and subtypes of 1p19q co-deleted gliomas [8]. Law et al. described the potential of using perfusion and spectroscopy in glioma stratification [6].

Even though in literature, 1p19q codeleted oligodendrogliomas are often described as having lower grades and carrying a good prognosis compared to their 1p19q non-codeleted astrocytoma and IDH wild counterparts. That may not always be true. Grade 4 gliomas in IDH mutant 1p19q non-codeleted gliomas have been described in cIMPACT studies and in WHO 2021. Unfortunately, high-grade 1p19q codeleted gliomas do not have much literature on genetic or radiological studies except from a few like Kapoor et al., which were done before WHO 2016 classification [8]. Therefore, Recently published glioma stratification literature doesn't consider these subgroups of gliomas[10].

Our case shows the value of advanced imaging in predicting the high-grade nature of glioma. Even the histopathology and first-order genetic markers did not predict higher grades initially. Our case demonstrates that CDKN2A/B mutation and other genetic markers should be evaluated, especially when radiological features support high grade, even if genetic glioma is IDH mutant 1p19q codeleted [7]. Biopsy sometimes is limited by the tissue sample and site of the biopsy; in literature, almost 2 to 9% of brain biopsies are non-diagnostic [11] [12]. Even though it has been suggested the second biopsy can be useful [13], unfortunately, it was not the case with our patient. This case also shows the value of accessing more detailed genetic markers when histology assessment is limited by sample. Right now, CDKN2A/B is performed only in doubtful cases in our institution, and this case shows it should become more generalized, especially when advanced imaging is collaborative.

Vera Androva:

Thank you for publishing these studies online. Regards, Vera Send flowers to Russia