Assessing tumor microstructure with time‐dependent diffusion imaging: Considerations and feasibility on clinical MRI and MRI‐Linac DOI Creative Commons
Minea Jokivuolle, Faisal Mahmood, Kristoffer H. Madsen

et al.

Medical Physics, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 10, 2024

Abstract Background Quantitative imaging biomarkers (QIBs) can characterize tumor heterogeneity and provide information for biological guidance in radiotherapy (RT). Time‐dependent diffusion MRI (TDD‐MRI) derived parameters are promising QIBs, as they describe tissue microstructure with more specificity than traditional diffusion‐weighted (DW‐MRI). Specifically, TDD‐MRI about both restricted diffusional exchange, which the two time‐dependent effects affecting tissue, relevant tumors. However, exhaustive modeling of require long acquisitions complex model fitting. Furthermore, several introduced measurements high gradient strengths and/or waveforms that possibly not available RT settings. Purpose In this study, we investigated feasibility a simple analysis framework detection exchange signal. To promote clinical applicability, use standard on conventional 1.5 T system moderate strength ( G max = 45 mT/m), hybrid MRI‐Linac low 15 mT/m). Methods Restricted were simulated geometries mimicking to investigate DW‐MRI signal behavior determine optimal experimental parameters. was implemented using pulsed field spin echo optimized MRI‐Linac. Experiments green asparagus 10 patients brain lesions performed evaluate (TDD) contrast source DW‐images. Results Simulations demonstrated how TDD able differentiate only dominating smaller cells from larger cells. The maximal simulations typical cancer cell sizes exceeded 5% but remained below particular, r 5–10 µm) or around 2% strength. measured MRI, found sub‐regions reflecting either compared noisy appearing white matter. Conclusions On system, maps showed consistent indicating different effects, potentially providing spatial heterogeneity. MRI‐Linac, same trends close measurement noise levels when common sizes. systems strengths, could be used tool identify include choosing biophysical specific characterization.

Language: Английский

Multiparametric MRI for characterization of the tumour microenvironment DOI
Emily Hoffmann, Max Masthoff, Wolfgang G. Kunz

et al.

Nature Reviews Clinical Oncology, Journal Year: 2024, Volume and Issue: 21(6), P. 428 - 448

Published: April 19, 2024

Language: Английский

Citations

20
Evaluating the Diagnostic Performance of MR Cytometry Imaging in Differentiating Benign and Malignant Breast Tumors DOI Open Access
Fan Liu, Lei Wu, Xinyi Luo

et al.

Journal of Magnetic Resonance Imaging, Journal Year: 2025, Volume and Issue: unknown

Published: March 11, 2025

ABSTRACT Background MR cytometry is a class of diffusion‐MRI‐based methods that characterize tumor microstructures at the cellular level. It involves multicompartmental biophysical modeling multi‐b and multiple diffusion time data to generate microstructural parameters, which may improve differentiation benign malignant breast tumors. Purpose To implement imaging with transcytolemmal water exchange (JOINT EXCHANGE) differentiate tumors, compare classification efficacy IMPULSED, JOINT, EXCHANGE. Study Type Prospective. Subjects 115 patients pathologically confirmed tumors (25 90 malignant). Field Strength/Sequence 3T; pulsed gradient spin‐echo (PGSE) diffusion‐weighted (DWI) oscillating (OGSE) DWI 25 50 Hz. Assessment Tumor regions were delineated by two radiologists on DWI. Time‐dependent ADC parameters (cell diameter , intracellular volume fraction rate constant extracellular diffusivity intrinsic ) calculated. Classification performance was assessed in original cohort an age‐adjusted (excluding older eliminate significant age differences). Statistical Tests Mann–Whitney U‐tests compared values. Multivariable logistic regression used stepwise approach based likelihood ratio test. The area under receiver operating characteristic (AUC) computed using DeLong Results In full analysis benign, malignant), from incorporating demonstrated superior (AUC: ADC, 0.822; 0.840; 0.902; EXCHANGE, 0.905). Combining different metrics further improved IMPULSED [, ], 0.942; JOINT 0.956; EXCHANGE 0.954; [], 0.927). These improvements also observed 42 Data Conclusion outperformed distinguishing Incorporating into its diagnostic performance. Evidence Level: 1 Technical Efficacy: Stage 2

Language: Английский

Citations

1
Advanced Diffusion‐Weighted MRI for Cancer Microstructure Assessment in Body Imaging, and Its Relationship With Histology DOI
Ella P. Fokkinga,

Juan A. Hernández‐Tamames,

Andrada Ianuş

et al.

Journal of Magnetic Resonance Imaging, Journal Year: 2023, Volume and Issue: 60(4), P. 1278 - 1304

Published: Nov. 30, 2023

Diffusion‐weighted magnetic resonance imaging (DW‐MRI) aims to disentangle multiple biological signal sources in each voxel, enabling the computation of innovative maps tissue microstructure. DW‐MRI model development has been dominated by brain applications. More recently, advanced methods with high fidelity histology are gaining momentum other contexts, for example, oncological applications body imaging, where new biomarkers urgently needed. The objective this article is review state‐of‐the‐art (ie, not including nervous system) oncology, and analyze its value as compared reference colocalized measurements, given that demonstrating histological validity any method essential. In article, we current landscape techniques extend standard apparent diffusion coefficient (ADC), describing their acquisition protocols, models, fitting settings, microstructural parameters, relationship histology. Preclinical, clinical, in/ex vivo studies were included. most used intravoxel incoherent motion (IVIM; 36.3% techniques), kurtosis (DKI; 16.7%), vascular, extracellular, restricted cytometry tumors (VERDICT; 13.3%), parameters using limited spectrally edited (IMPULSED; 11.7%). Another notable category relates b ‐tensor encoding or joint diffusion‐relaxometry. reviewed approaches provide histologically meaningful indices cancer microstructure (eg, vascularization/cellularity) which, while necessarily accurate numerically, may still useful sensitivity microscopic pathological processes. Future work community should focus on improving inter‐/intra‐scanner robustness, assessing broader contexts. Level Evidence NA Technical Efficacy Stage 2

Language: Английский

Citations

13
Profiling specific cell populations within the inflammatory tumor microenvironment by oscillating-gradient diffusion-weighted MRI DOI Creative Commons
Emily Hoffmann, Mirjam Gerwing, Stephan Niland

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2023, Volume and Issue: 11(3), P. e006092 - e006092

Published: March 1, 2023

Background The inflammatory tumor microenvironment (TME) is formed by various immune cells, being closely associated with tumorigenesis. Especially, the interaction between tumor-infiltrating T-cells and macrophages has a crucial impact on progression metastatic spread. purpose of this study was to investigate whether oscillating-gradient diffusion-weighted MRI (OGSE-DWI) enables cell size-based discrimination different populations TME. Methods Sine-shaped OGSE-DWI combined Imaging Microstructural Parameters Using Limited Spectrally Edited Diffusion (IMPULSED) approach measure microscale diffusion distances, here relating sizes. accuracy IMPULSED-derived radii evaluated using in vitro spheroid models, consisting either pure cancer macrophages, or T-cells. Subsequently, vivo experiments aimed assess changes within TME its specific composition syngeneic murine breast models divergent degrees malignancy (4T1, 67NR) during progression, clodronate liposome-mediated depletion checkpoint inhibitor (ICI) treatment. Ex analysis conducted immunohistochemical wheat germ agglutinin staining membranes, while intratumoral analyzed CD3 F4/80 co-staining. Results detected mean 8.8±1.3 µm for 4T1, 8.2±1.4 67NR, 13.0±1.7 macrophage, 3.8±1.8 T-cell spheroids. While infiltration 4T1 tumors observed decreasing from 9.7±1.0 5.0±1.5 µm, increasing amount 67NR resulted 8.9±1.2 12.5±1.1 µm. After macrophage depletion, decreased 6.3±1.7 4.4±0.5 after ICI treatment captured both more pronounced effects model. Conclusions provides versatile tool non-invasive profiling assessing dominating type macrophages.

Language: Английский

Citations

12
Cellular Exchange Imaging (CEXI): Evaluation of a diffusion model including water exchange in cells using numerical phantoms of permeable spheres DOI Creative Commons
Rémy Gardier,

Juan Luis Villarreal Haro,

Erick J. Canales‐Rodríguez

et al.

Magnetic Resonance in Medicine, Journal Year: 2023, Volume and Issue: 90(4), P. 1625 - 1640

Published: June 6, 2023

Purpose Biophysical models of diffusion MRI have been developed to characterize microstructure in various tissues, but existing are not suitable for tissue composed permeable spherical cells. In this study we introduce Cellular Exchange Imaging (CEXI), a model tailored cells, and compares its performance related Ball & Sphere (BS) that neglects permeability. Methods We generated DW‐MRI signals using Monte‐Carlo simulations with PGSE sequence numerical substrates made cells their extracellular space range membrane From these signals, the properties were inferred both BS CEXI models. Results outperformed impermeable by providing more stable estimates cell size intracellular volume fraction time‐independent. Notably, accurately estimated exchange time low moderate permeability levels previously reported other studies (). However, highly (), parameters less stable, particularly coefficients. Conclusion This highlights importance modeling quantify cellular substrates. Future should evaluate clinical applications such as lymph nodes, investigate potential biomarker tumor severity, develop appropriate account anisotropic membranes.

Language: Английский

Citations

12
Diffusion MRI with free gradient waveforms on a high-performance gradient system: Probing restriction and exchange in the human brain DOI Creative Commons
Arthur Chakwizira, Ante Zhu, Thomas Foo

et al.

NeuroImage, Journal Year: 2023, Volume and Issue: 283, P. 120409 - 120409

Published: Oct. 13, 2023

The dependence of the diffusion MRI signal on time carries signatures restricted and exchange. Here we seek to highlight these in human brain by performing experiments using free gradient waveforms that are selectively sensitive two effects. We examine six healthy volunteers both strong ultra-strong gradients (80, 200 300 mT/m). In an experiment featuring a large set with different sensitivities exchange (150 samples), our results reveal unique time-dependence grey white matter, where former is characterised latter predominantly exhibits diffusion. Furthermore, show independently varying can be used map brain. consistently find matter at least twice as fast across all subjects strengths. shortest times observed this study were cerebellar cortex (115 ms). also assess feasibility future clinical applications method work, grey-white contrast obtained 25-minute mT/m protocol preserved 4-minute 10-minute 80 protocol. Our work underlines utility for detecting due vivo, which may potentially serve tool studying diseased tissue.

Language: Английский

Citations

11
Time-dependent diffusion MRI and kinetic heterogeneity as potential imaging biomarkers for diagnosing suspicious breast lesions with 3.0-T breast MRI DOI
Xue Li,

Chunmei Li,

Bin Hua

et al.

Magnetic Resonance Imaging, Journal Year: 2025, Volume and Issue: 117, P. 110323 - 110323

Published: Jan. 5, 2025

Language: Английский

Citations

0
Longitudinal changes of blood-brain barrier and transcytolemmal water exchange permeability in Alzheimer's disease mice: A non-contrast MRI study DOI Creative Commons
Chengjie Xiong, Ziyang Yu,

Yin Yu

et al.

NeuroImage, Journal Year: 2025, Volume and Issue: unknown, P. 121141 - 121141

Published: March 1, 2025

Growing evidence suggests that Alzheimer's disease (AD) has been linked with the dysfunction of glymphatic system. Previous studies were primarily cross-sectional and focused on only one specific component, hindering understanding overall function in AD. We evaluated longitudinal changes multiple components system (blood-brain barrier (BBB) transcytolemmal water exchange (TWE) permeability) AD mice. Five female wild-type four 3 × Tg-AD mice from 5 to 13 months age scanned monthly using two non-contrast MRI techniques, water-extraction-with-phase-contrast-arterial-spin-tagging (WEPCAST) diffusion-time-dependent kurtosis imaging (tDKI), yielding BBB TWE permeability. Immunostaining was used evaluate tight junction proteins associated structural integrity, aquaporin 4 (AQP4) related TWE, AQP4 perivascular space (PVS) polarization might represent PVS-parenchyma exchange. The relationship between pathology, as measured by amyloid beta (Aβ) tau deposition, also explored. Our results revealed significantly increased hippocampal permeability mouse brains, consistent histological findings reduced upregulated AQP4, which correlated each other can be predictive Aβ deposition. Impaired PVS found In conclusion, altered mice, these vivo validated pathologically, affect waste clearance neurofluid.

Language: Английский

Citations

0
Imaging Microstructural Parameters of Breast Tumor in Patient Using Time-Dependent Diffusion: A Feasibility Study DOI Creative Commons
Shuyi Peng, Peng Sun, Jie Liu

et al.

Diagnostics, Journal Year: 2025, Volume and Issue: 15(7), P. 823 - 823

Published: March 24, 2025

Objectives: To explore the feasibility of time-dependent diffusion in clinical applications breast MRI, as well capacity quantitative microstructural mapping for characterizing cellular properties malignant and benign tumors. Methods: 38 patients with 45 lesions were enrolled. Diffusion MRI acquisition was conducted a combination pulsed gradient spin-echo sequences (PGSE) oscillating (OGSE) on 3T scanner. The parameters including cellularity extracellular diffusivity (Dex), mean cell size, intracellular volume fraction (νin), apparent coefficient (ADC) values calculated. Each parameter compared using unpaired t-test between area under receiver operating characteristic curve (AUC) used to evaluate diagnostic performance different indices. Results: diameter, Dex, ADC0Hz, ADC25Hz, ADC50Hz significantly lower group than (p < 0.001), while νin higher 0.001). All ADC achieved high accuracy differentiating tumors breast. For parameters, AUC greater others (AUC = 0.936). In an immunohistochemical subgroup comparison, PR-positive had cellularity, elevated Dex ADC0Hz negative groups 0.05). When combining (cellularity, ADC25Hz), highest obtained 0.969. Conclusions: DWI short time is capable providing additional have potential serve non-invasive tool probe differences internal structures lesions.

Language: Английский

Citations

0
When CEST meets diffusion: Multi‐echo diffusion‐encoded CEST (dCEST) MRI to measure intracellular and extracellular CEST signal distributions DOI Creative Commons
Sultan Z. Mahmud, Hye‐Young Heo

Magnetic Resonance in Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Abstract Purpose To develop a multi‐echo, diffusion‐encoded chemical exchange saturation transfer (dCEST) imaging technique for estimating the intracellular and extracellular/intravascular contributions to conventional CEST signal. Methods A dCEST pulse sequence was developed quantify signal fractions, transverse relaxation times (T 2 ), apparent diffusion coefficient (ADC) of water compartments. images were acquired across wide range TE, b‐values, RF strengths, frequency offsets. The data analyzed using two‐compartment model with distinct diffusivities T values. Intracellular extracellular fractions water‐saturation spectra (Z‐spectra) corresponding amide proton (APT) signals estimated from human brain scans healthy volunteers at 3 T. Results multi‐echo results showed that significantly higher than whereas values shorter those ADC compartment lower compartment. analysis average Z‐spectra 85 ± 7% 15 4%, respectively. overall APT‐weighted total (i.e., + extracellular) Conclusions provides valuable insight into source in MRI, offering potential utility clinical applications.

Language: Английский

Citations

0