# Inside-Out Nonlinear Gradients to Improve Diffusion MRI

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $383,156

## Abstract

Project Summary/Abstract
The lifetime risk of prostate cancer is 1 in 9 and it remains the 2nd leading cancer killer of men. Yet many
patients with low grade disease receive premature or excessive treatment, which can lead to decades of
incontinence and erectile dysfunction. One reason for the simultaneous over- and under- diagnosis of prostate
cancer is that current imaging methods are unreliable, which in turn make biopsies unreliable. A noninvasive
imaging method with good sensitivity and specificity is one of the greatest needs in prostate cancer
management, and diffusion weighted MRI (DWI) is the most promising candidate. However, prostate MRI has
extremely low image quality due to the long echo times needed for adequate diffusion encoding.
To improve DWI of prostate, we introduce a new concept in MRI hardware: an accessory whose sole purpose
is to provide diffusion encoding to a target organ. Unlike imaging gradients which are volume-encompassing
and stringently linear, this “inside-out” diffusion gradient is a wand placed between the upper legs which
creates strong nonlinear fields at the prostate. The geometry allows for standard spatial encoding, standard
receiver placement, and portability between scanners.
For prostate imaging, this approach achieves a gradient that is >10-fold stronger over the region of interest,
increasing both overall SNR and sensitivity to epithelial/cellular volume, a hallmark of malignancy. The
increase in field strength is predicted to double contrast in DWI of prostate, improving active surveillance,
biopsy hit rates, and treatment monitoring. Taken together, the preliminary data on (1) achievable hardware
specs, (2) prostate imaging simulations, and (3) phantom experimental results make a strong case for the
feasibility of this project and the significant impact it will have on prostate DWI.
Approach:
Aim 1 will install and characterize a custom diffusion gradient to demonstrate DWI in a prostate lesion phantom
which is consistent with conventional methods, but with higher reproducibility and CNR.
Aim 2 applies the new method to prostate of healthy controls to establish positioning, PNS thresholds,
accuracy, and improved image quality (precision, contrast, reproducibility and qualitative ratings) in vivo.
Aim 3 will image patients with biopsy-naïve suspected lesions, which will be outlined and scored by multiple
radiologists to quantify contrast, diagnostic confidence and inter-reader variability in a realistic population.
Aim 4 will acquire, in radical prostatectomy patients, coregistered presurgical in vivo MRI, ex vivo MRI of the
excised prostate, and whole-mount pathology to show correlation between ADC and true Gleason score.
Together, these aims will provide strong evidence for the increased precision, contrast, diagnostic confidence,
and clinical validity of DWI acquired with this hardware.

## Key facts

- **NIH application ID:** 10311360
- **Project number:** 1R01CA264851-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** GIGI GALIANA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $383,156
- **Award type:** 1
- **Project period:** 2021-07-06 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10311360

## Citation

> US National Institutes of Health, RePORTER application 10311360, Inside-Out Nonlinear Gradients to Improve Diffusion MRI (1R01CA264851-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10311360. Licensed CC0.

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