Therapy Monitoring with Functional and Molecular MR Imaging

Tumour heterogeneity poses a significant challenge for treatment stratification. The goals of this study were to quantify heterogeneity in hepatocellular carcinoma (HCC) using multiparametric magnetic resonance imaging (mpMRI), and to report preliminary data correlating quantitative MRI parameters with advanced histopathology and gene expression in a patient subset. Thirty-two HCC patients with 39 HCC lesions underwent mpMRI including diffusion-weighted imaging (DWI), blood-oxygenation-level-dependent (BOLD), tissue-oxygenation-level-dependent (TOLD) and dynamic contrast-enhanced (DCE)-MRI. Histogram characteristics [central tendency (mean, median) and heterogeneity (standard deviation, kurtosis, skewness) MRI parameters] in HCC and liver parenchyma were compared using Wilcoxon signed-rank tests. Histogram data was correlated between MRI methods in all patients and with histopathology and gene expression in 14 patients. HCCs exhibited significantly higher intra-tissue heterogeneity vs. liver with all MRI methods (P < 0.030). Although central tendency parameters showed significant correlations between MRI methods and with each of histopathology and gene expression, heterogeneity parameters exhibited additional complementary correlations between BOLD and DCE-MRI and with histopathologic hypoxia marker HIF1α and gene expression of Wnt target GLUL, pharmacological target FGFR4, stemness markers EPCAM and KRT19 and immune checkpoint PDCD1. Histogram analysis combining central tendency and heterogeneity mpMRI features is promising for non-invasive HCC characterization on the imaging, histologic and genomics levels.

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“…There are a few published reports on the use of imaging to predict and assess immunotherapy outcome 51 . Jajamovich et al .…”

Section: Discussionmentioning

confidence: 99%

Quantification of hepatocellular carcinoma heterogeneity with multiparametric magnetic resonance imaging

Hectors

Wagner

Bane

et al. 2017

Sci Rep

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“…So, according to literature, on the value of the functional data obtained in CT and PET, compared with only morphological data in CT and MRI, to evaluate the response to ECT, it appears more appropriate to use Choi or PERCIST Criteria, although it would be better to link the two data[22-26,34-40]. García-Figueiras et al[24] demonstrated that standard imaging modalities and current morphologic response criteria do not always offer the adequate information for early therapy assessment, especially when target or ablated therapy were considered. According to García-Figueiras et al[24], MRI is able to predict treatment success before size changes become evident, thanks its capability to integrate anatomic, physiologic, and functional tissue information, which may overcome these limitations.…”

Section: Discussionmentioning

confidence: 99%

“…García-Figueiras et al[24] demonstrated that standard imaging modalities and current morphologic response criteria do not always offer the adequate information for early therapy assessment, especially when target or ablated therapy were considered. According to García-Figueiras et al[24], MRI is able to predict treatment success before size changes become evident, thanks its capability to integrate anatomic, physiologic, and functional tissue information, which may overcome these limitations. In our study the morphologic information obtained by MRI examination did not show a dimensional change of treated pancreas lesion neither no statistically-significant difference of signal intensity obtained from T1-weighted images, T2-weighted images and equilibrium-phase of contrast MR study.…”

Section: Discussionmentioning

confidence: 99%

“…Objective therapeutic responses according to RECIST 1.1 are as follows: complete remission (CR) is disappearance of target lesion for at least 4 wk; partial remission (PR) is a decline of at least 30% in tumor diameter; stable disease (SD) is neither PR nor progressive disease (PD); and PD is at least a 20% increase in tumor diameter and 5-mm absolute increase was required. Moreover for CT images, the response to ECT was evaluated according the Choi criteria[24]: CR is disappearance of target lesion; PR is a decrease in tumor size ≥ 10% or decrease in tumor density ≥ 15% on CT; SD is neither PR nor PD; and PD is an increase in tumor size ≥ 10% and does not meet PR criteria by tumor density.…”

Section: Methodsmentioning

confidence: 99%

“…Currently, standard imaging techniques and morphologic response criteria do not provide the necessary information to evaluate tumor response. Magnetic resonance imaging (MRI) offers a combination of anatomic, physiologic, and molecular information, which may overcame these limitations, and is being increasingly used for therapy response assessment[23,24]. …”

Section: Introductionmentioning

confidence: 99%

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Early radiological assessment of locally advanced pancreatic cancer treated with electrochemotherapy

Granata¹,

Fusco²,

Setola³

et al. 2017

WJG

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AIMTo report early imaging assessment of ablated area post electrochemotherapy (ECT) in patients with locally advanced pancreatic cancer (LAPC).METHODSECT was performed in 19 LAPC patients enrolled in an approved ongoing clinical phase I/II study. Before and after ECT, 18 patients underwent computed tomography (CT) scan, 11 patients underwent morphological and functional magnetic resonance (MR) scan (dynamic contrast enhanced-MRI) calculating wash-in slope (WIS) and wash-out slope (WOS); diffusion weighted imaging calculating pseudo-diffusivity (Dp), perfusion fraction (fp) and tissue diffusivity (Dt); 10 patients underwent positron emission tomography (PET). Response evaluation criteria in solid tumour (RECIST) on MR and CT were used to assess tumour therapy response. Choi on CT, PET response criteria in solid tumors (PERCIST) on PET and functional parameters on MR were used to evaluate treatment response.RESULTSFor each patient no significant reduction was measurable by CT and MR using RECIST. According Choi criteria a partial response was obtained in 18/18 (100.0%) patients. According PERCIST criteria 6/10 (60.0%) patients showed a partial response, 3/10 (30.0%) stable disease and 1/10 (10.0%) progression disease. Moreover, using functional MR parameters, a significant reduction of viable tumour after ECT can be observed. According ΔWIS and ΔWOS 9/11 (81.8%) patients exhibited a partial response and 2/11 (18.2%) stable disease; 8/11 (72.7%) patients were considered in partial response by ΔDp evaluation and 3/11 (27.3%) in stable disease; according ΔDt 7/11 (63.6%) patients showed a partial response, 1/11 (9.1%) showed progression of disease and 3/11 (27.3%) were stable. Perfusion fraction fp showed a significant reduction after ECT only in four patients. No significant difference was observed after ECT in signal intensity of T1-weighted images and T2-weighted images, and in equilibrium-phase of contrast study, according to χ2 test was observed. A good correlation was reported between ΔHounsfield unit and Δmaximum standardized uptake value and between Δfp and ΔWOS, with a significant statistically difference (P < 0.05) using Spearman correlation coefficient.CONCLUSIONPerfusion and diffusion MR derived parameters, Choi, PERCIST criteria are more performant than morphological MR and CT criteria to assess ECT treatment response.

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Peptide‐Enabled Thrombus‐Targeting Nanoparticles for Highly Effective Targeted CT Imaging and Eradication of Thrombi

Bao

Miao

et al. 2023

Adv Funct Materials

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Thrombotic disease poses a significant threat to human health as it blocks blood vessels and leads to severe symptoms. Effective treatment requires targeted therapy and precise localization of the thrombus, but traditional drugs are limited in their targeting ability and ability to locate the thrombus. To overcome these issues, a nanoparticle capable of both thrombus targeting and computed tomography (CT) imaging is developed. Phage display technology is used to screen for the thrombus‐targeting peptide termed GK, which is then linked to the surface of macroporous silica (Mp‐SiO2) with a Bi core to create Mp‐Bi@SiO2‐GK. The large pores of Mp‐Bi@SiO2‐GK enable the transport of the drug Urokinase (UK), while the Bi core provides the capabilities of CT imaging and photothermal therapy. The Mp‐Bi@SiO2‐GK nanoparticles precisely target thrombi in mouse carotid arteries and locate them via CT imaging. Furthermore, the combination of Bi‐enabled photothermal therapy and UK‐induced chemotherapy enhance the thrombolysis efficiency. Treatment with Mp‐Bi@SiO2‐GK nanoparticles do not harm tissues/organs or affect liver/kidney metabolism. These results show that Mp‐Bi@SiO2‐GK exhibits precise thrombus targeting and efficient imaging/treatment capability, making it a promising tool for the diagnosis and treatment of thrombosis.

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Therapy Monitoring with Functional and Molecular MR Imaging

Cited by 31 publications

References 102 publications

Quantification of hepatocellular carcinoma heterogeneity with multiparametric magnetic resonance imaging

Quantification of hepatocellular carcinoma heterogeneity with multiparametric magnetic resonance imaging

Early radiological assessment of locally advanced pancreatic cancer treated with electrochemotherapy

Peptide‐Enabled Thrombus‐Targeting Nanoparticles for Highly Effective Targeted CT Imaging and Eradication of Thrombi

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