Use of MRI to Assess Pseudoprogression for Glioblastomas Research Paper

📌Category: Health, Illness, Medicine
📌Words: 818
📌Pages: 3
📌Published: 08 April 2022

The most common type of malignant growth in the central nervous system is a glioblastoma (GBM). [1] Post treatment, it is important to be able to differentiate whether the changed size of a tumour is caused by true progressive disease (PD), pseudoprogression, or tissue necrosis from the harsh treatment. Pseudoprogression is a non-malignant increase in lesion size that appears early post-treatment. On conventional magnetic resonance imaging (MRI), the tumour seems homogenous and growing. In order to be completely certain, there is need for other, more exact methods of differentiating the tissue in order to know whether to use more intense treatments, or to confirm that the current treatment is working.  

Perfusion MRI and MR Spectroscopy

Two of such imaging techniques are perfusion MRI and MR spectroscopy (MRS):

Perfusion MRI is a part of the GBM post-treatment follow-up. The primary method used for brain tumour perfusion MRI is dynamic susceptibility contrast (DSC). DSC relies on T2 ef-fects of gadolinium-based contrast agents and is injected intravenously. The main parameter derived from DSC is the relative cerebral blood volume (rCBV). Pseudoprogressed areas have lower rCBV compared to true PD [2]. MRS compares the chemical composition of normal brain tissue with abnormal brain tissue. The MRS is a series of tests that are added to the MRI scan and measures the chemical metabolism of a suspected tumour. MRS works by utilizing that the distribution of electrons within an atom causes nuclei in the different molecules to experience slightly different magnetic fields. This then results in slightly different resonant frequencies that return slightly different signals. MRS can therefore distinguish between tu-mour recurrence, radiation necrosis and pseudo-progression.

Clinical Use

DSC perfusion and MRS are two different methods used to differentiate between true PD and pseudoprogression. The two methods are visually very different. For DSC perfusion a rCBV map is made. The contrast agent is activated when perfusing active tissue and lights up as a result. Here, the inactive tissue of the pseudoprogression remains dark, and the malignant GBM can be mapped out. This is evident in fig. 1, where the true tumour PD has high vascu-larity compared to the pseudoprogressive tissue.

Figure 1; L: Conventional post-contrast MRI. R: Neuro standardized rCBV map. [4]

With MRS the visual is a graph. For GBM the graph shows a low lipid signal, as well as a high choline/N-acetyl-aspartate (NAA) ratio. In comparison, a patient with pseudoprogression would show elevated lipid signals, as well as an absence of choline or a low choline/NAA ratio. [3] This can be seen in fig. 2, where the MRS is used to investigate the chemical struc-ture of the pseudoprogression of a GBM in the left parietal lobe.

Figure 2; MRS of progressive disease and pseudoprogression. A) MRS shows marked elevation of the cho-line/NAA ratio, typical for a malignant tumour, therefore indicating progressive disease. B) Pseudoprogression after treatment of a GBM. Also shows elevation of choline/NAA ratio, which exemplifies overlap with progres-sive disease. The lipid/lactate peak is highly elevated. [5]

Method Analysis

A meta-analysis that included 35 studies showed that MRS had the highest diagnostic accura-cy in detection of tumour progression followed by perfusion MRI. However, perfusion MRI is more common in clinical use whereas MRS is used for specific indications [6]. One of the reasons the accuracy of MRI perfusion is inferior to MRS is due to contrast leak into necrotic tissue. The gadolinium-based contrast of MRS is rapidly cleared from the circulation due to the disruption of the blood-brain barrier which is a side-effect of chemoradiotherapy and the angiogenesis incurred by tumours. This leads to rCBV incorrectly estimating the lesions size and incidentally the rCBV value. MRS’s limitations is that applying universally accepted ratios for evaluating pseudoprogression is difficult due to different MRI strengths and imag-ing protocols. Furthermore, MRS is very susceptible to artifacts. This disturbs the imaging process and therefore the assessment of the tissue [7]. A general conclusion of which method is best is hard to evaluate. Even though the meta-analysis concluded the preferred method the analysis only consisted of 35 studies. Further research is needed.

References

[1] - Bleeker, F. E., Molenaar, R. J., & Leenstra, S. (2012). Recent advances in the molecular understanding of glioblastoma. Journal of Neuro-Oncology, 108(1), 11–27. https://doi.org/10.1007/s11060-011-0793-0 (Last visited: 07.03.22)

[2] - Thust, S. C., van den Bent, M. J., & Smits, M. (2018). Pseudoprogression of brain tumors. Journal of Magnetic Resonance Imaging, 48(3), 571–589. https://doi.org/10.1002/jmri.26171  (Last visited: 07.03.22).

[3] - Sawlani, V., Taylor, R., Rowley, K., Redfern, R., Martin, J., & Poptani, H. (2012). Magnetic Resonance Spectroscopy for Differentiating Pseudo-Progression from True Progression in GBM on Concurrent Chemora-diotherapy. The Neuroradiology Journal, 25(5), 575–586. https://doi.org/10.1177/197140091202500511  (Last visited: 07.03.22).

[4] - Imaging Biometrics. (n.d.). NEURO-ONCOLOGY SOLUTIONS, from https://www.imagingbiometrics.com/neuro-oncology-solutions/  (Last visited: 07.03.22). Fig.3.

[5] - Leao, D., Craig, P., Godoy, L., Leite, C., & Policeni, B. (2019). Response Assessment in Neuro-Oncology Criteria for Gliomas: Practical Approach Using Conventional and Advanced Techniques. American Journal of Neuroradiology, 41(1), 10–20. https://doi.org/10.3174/ajnr.a6358 (Last visited: 07.03.22). Fig. 10.

[6] - Zikou, A., Sioka, C., Alexiou, G. A., Fotopoulos, A., Voulgaris, S., & Argyropoulou, M. I. (2018). Radia-tion Necrosis, Pseudoprogression, Pseudoresponse, and Tumor Recurrence: Imaging Challenges for the Evalua-tion of Treated Gliomas. Contrast Media & Molecular Imaging, 2018, 1–6. https://doi.org/10.1155/2018/6828396 (Last visited: 08.03.22).

[7] - Abdulla, S., Saada, J., Johnson, G., Jefferies, S., & Ajithkumar, T. (2015). Tumour progression or pseudo-progression? A review of post-treatment radiological appearances of glioblastoma. Clinical Radiology, 70(11), 1299–1312. https://doi.org/10.1016/j.crad.2015.06.096 (Last visited: 08.03.22).

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