[Paper Review] Magnetic resonance imaging of mean cell size in human breast tumors

Junzhong Xu, Xiaoyu Jiang+9 more|arXiv (Cornell University)|May 19, 2019

Advanced MRI Techniques and ApplicationsMedicine48 references17 citations

TL;DR

This study introduces IMPULSED, a fast, clinically feasible MRI method that enables non-invasive in vivo mapping of mean cell size in human breast tumors using standard 3T MRI scanners. By combining spectrally edited diffusion-weighted imaging with analytical models of gradient waveforms, IMPULSED achieves high-resolution (1.3 mm in-plane) cell size maps in ~7 minutes, validated across simulations, in vitro cell experiments, and in vivo animal models, with successful application in pre-operative breast cancer patients.

ABSTRACT

Purpose: Cell size is a fundamental characteristic of all tissues, and changes in cell size in cancer reflect tumor status and response to treatments, such as apoptosis and cell cycle arrest. Unfortunately, cell size can only be obtained by pathologic evaluation of the tumor in the current standard of care. Previous imaging approaches can be implemented on only animal MRI scanners or require relatively long acquisition times that are undesirable for clinical imaging. There is a need to develop cell size imaging for clinics. Experimental Design: We propose a new method, IMPULSED (Imaging Microstructural Parameters Using Limited Spectrally Edited Diffusion) that can characterize mean cell sizes in solid tumors. We report the use of combined sequences with different gradient waveforms on human MRI and analytical equations that link DWI signals of real gradient waveforms and specific microstructural parameters such as cell size. We also describe comprehensive validations using computer simulations, cell experiments in vitro, and animal experiments in vivo and finally demonstrate applications in pre-operative breast cancer patients. Results: With fast acquisitions (~ 7 mins), IMPULSED can provide high-resolution (1.3 mm in-plane) mapping of mean cell size of human tumors in vivo on currently-available 3T MRI scanners. All validations suggest IMPULSED provide accurate and reliable measurements of mean cell size. Conclusion: The proposed IMPULSED method can assess cell size variations in the tumor of breast cancer patients, which may have the potential to assess early response to neoadjuvant therapy.

Motivation & Objective

• To develop a clinically viable MRI method for non-invasive assessment of mean cell size in solid tumors.
• To overcome limitations of existing methods that require specialized scanners or long scan times.
• To enable in vivo, high-resolution cell size mapping in human breast tumors using standard clinical MRI hardware.
• To validate the method across multiple platforms: computer simulations, in vitro cell cultures, and in vivo animal models.
• To translate the method into clinical application for pre-operative breast cancer patients.

Proposed method

• IMPULSED employs a combination of diffusion-weighted imaging (DWI) with spectrally edited gradient waveforms to isolate microstructural signals related to cell size.
• The method uses analytical equations that relate the DWI signal from real gradient waveforms to microstructural parameters, including mean cell size.
• It leverages limited spectral editing to enhance sensitivity to intracellular compartment size while minimizing scan time.
• The sequence design enables rapid acquisition (~7 minutes) with high spatial resolution (1.3 mm in-plane) on standard 3T MRI scanners.
• Validation is performed through multi-scale benchmarks: numerical simulations, in vitro experiments with controlled cell suspensions, and in vivo animal tumor models.
• Clinical feasibility is demonstrated in pre-operative breast cancer patients using routine clinical MRI protocols.

Experimental results

Research questions

• RQ1 Can a clinically feasible MRI method accurately estimate mean cell size in human breast tumors without requiring specialized hardware?
• RQ2 How does the IMPULSED sequence perform in terms of accuracy and reproducibility across different biological scales (simulations, in vitro, in vivo)?
• RQ3 Can IMPULSED detect biologically relevant changes in cell size associated with tumor status and treatment response?
• RQ4 What is the achievable spatial resolution and scan time for in vivo mean cell size mapping on standard 3T MRI systems?
• RQ5 Does the method provide reliable and quantitative cell size estimates in a clinical setting with pre-operative breast cancer patients?

Key findings

• IMPULSED achieved high-resolution (1.3 mm in-plane) mean cell size mapping of human breast tumors in vivo with a scan time of approximately 7 minutes on standard 3T MRI scanners.
• Simulations confirmed the method’s sensitivity to cell size changes and robustness to noise and sequence imperfections.
• In vitro experiments with controlled cell suspensions demonstrated strong agreement between measured and expected cell sizes, validating the method’s accuracy.
• In vivo animal studies showed consistent and reproducible cell size maps in tumor-bearing models, confirming physiological relevance.
• Clinical application in pre-operative breast cancer patients successfully generated reliable cell size maps, demonstrating feasibility for routine clinical use.
• The method showed potential for detecting early treatment-induced changes in cell size, such as those associated with apoptosis or cell cycle arrest.