Mapping early tumor response to radiotherapy using diffusion kurtosis imaging**

Abstract

Purpose In this pilot study, DKI measures of diffusivity and kurtosis were compared in active tumor regions and correlated to radiologic response to radiotherapy after completion of 2 weeks of treatment to derive potential early measures of tumor response. Methods MRI and Magnetic Resonance Spectroscopic Imaging (MRSI) data were acquired before the beginning of RT (pre-RT) and 2 weeks after the initiation of treatment (during-RT) in 14 glioblastoma patients. The active tumor region was outlined as the union of the residual contrast-enhancing region and metabolically active tumor region. Average and standard deviation of mean, axial, and radial diffusivity (MD, AD, RD) and mean, axial, and radial kurtosis (MK, AK, RK) values were calculated for the active tumor VOI from images acquired pre-RT and during-RT and paired t-tests were executed to estimate pairwise differences. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive capabilities of changes in diffusion metrics for progression-free survival (PFS). Results Analysis showed significant pairwise differences for AD ( p = 0.035; Cohen’s d of 0.659) and AK ( p = 0.019; Cohen’s d of 0.753) in diffusion measures after 2 weeks of RT. ROC curve analysis showed that percentage change differences in AD and AK between pre-RT and during-RT scans provided an Area Under the Curve (AUC) of 0.524 and 0.762, respectively, in discriminating responders (PFS>180 days) and non-responders (PFS<180 days). Conclusion This pilot study, although preliminary in nature, showed significant changes in AD and AK maps, with kurtosis derived AK maps showing an increased sensitivity in mapping early changes in the active tumor regions.

Robust, fast and accurate mapping of diffusional mean kurtosis

“…Nonetheless, we can point to a few recent examples where the measurement of directional kurtosis has clear advantages. A study on mapping tumour response to radiotherapy treatment found axial kurtosis to provide the best sensitivity to treatment response (Goryawala et al, 2022 ). In a different study a correlation was found between glomerular filtration rate and axial kurtosis is assessing renal function and interstitial fibrosis (Li et al, 2022a ).…”

“…Recent clinical benefits of using kurtosis metrics over other DW-MRI derived measures have been demonstrated for grading hepatocellular carcinoma (Li et al, 2022b ), prognosing chronic kidney disease (Liu et al, 2021 ), differentiating parotid gland tumours (Huang et al, 2021a ), measuring response to radiotherapy treatment in bone tumour (Guo et al, 2022a ) and glioblastoma (Goryawala et al, 2022 ), identifying tissue abnormalities in temporal lobe epilepsy patients with sleep disorders (Guo et al, 2022b ) and brain microstructural changes in mild traumatic brain injury (Wang et al, 2022 ), monitoring of renal function and interstitial fibrosis (Li et al, 2022a ), detecting the invasiveness of bladder cancer into muscle (Li et al, 2022d ), aiding management of patients with depression (Maralakunte et al, 2022 ), delineating acute infarcts with prognostic value (Hu et al, 2022 ), predicting breast cancer metastasis (Zhou et al, 2022 ), diagnosing Parkinson's disease (Li et al, 2022c ), amongst others reported prior and not listed here.…”

Biomarker-driven molecular imaging probes in radiotherapy

“…Furthermore, with improved characterizations of the biological response of tumors to treatment methods, particularly, radiotherapy with immunomodulatory effects, advanced and efficacious therapeutic strategies might be developed. In clinical attempts and preclinical studies, several biological imaging techniques, such as diffusion kurtosis imaging 137 , multi-parametric MRI 138 , and highly sensitive whole-body PET/SPECT or optical imaging 139 , have been trialed or tested to assess early tumor response to radiotherapy, concentrating on the level of cellular communities and acellular components.…”