Davide Prezzi1, Radhouene Neji2,3, James J Stirling3, Sami Jeljeli3, Hema Verma4, Tim O'Brien5, Benjamin Challacombe5, Archana Fernando5, Ashish Chandra6, Vicky Goh1, and Ralph Sinkus7
1Cancer Imaging, King's College London, London, United Kingdom, 2MR Research Collaborations, Siemens Healthcare, Frimley, United Kingdom, 3King's College London, London, United Kingdom, 4Radiology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom, 5Urology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom, 6Pathology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom, 7Biomedical Engineering, King's College London, London, United Kingdom
Synopsis
Incidentally
detected renal tumors are overtreated surgically: up to 20% of them are benign,
most frequently oncocytomas. We hypothesize that integrating biomechanical assessment
with functional/morphological MRI can improve lesion characterization,
precluding unnecessary surgery. Initial experience in 5 resected renal
oncocytomas and 13 renal cell carcinomas (RCC) demonstrates that MR
Elastography (MRE) at 30Hz with shear modulus parametric mapping is feasible
and adds value within a multiparametric MRI assessment: oncocytoma displays
higher median shear attenuation (α) and lower shear velocity (C) than RCC. MRE
parameters appear to be stronger classifiers than quantitative DCE MRI
parameters (Ktrans, kep), ADC and T2 signal intensity.
Purpose
- To assess the feasibility of 3T Magnetic Resonance
Elastography (MRE) for characterizing renal tumors with surgical pathology as
the gold standard, in particular for distinguishing renal oncocytoma from RCC.
- To correlate tumor
MRE parametric mapping with same-level quantitative functional and anatomical imaging,
including tumor DCE MRI parameters, apparent diffusion coefficient (ADC) and T2
signal intensity.
Background
With the growing use of
cross-sectional imaging, incidental detection of asymptomatic small renal
tumors (less than 4 cm) has risen steadily1,2. Although most of
these lesions represent renal cell carcinoma (RCC), up to 20% are benign3.
A recent estimate suggests that ~5600 benign renal tumors undergo surgical resection
yearly in the US4. Renal oncocytoma is the most common benign
lesion, accounting for ~15% of all renal tumors; conventional imaging cannot
differentiate oncocytoma from RCC reliably5,6. Oncocytoma has a
characteristic macroscopic appearance of a homogenous dark brown lesion with frequent central scar and absence of necrosis. Microscopically it consists of
tight cellular nests surrounded by myxoid stroma. Conversely, clear cell RCC
(the most common subtype) consists of soft yellow material alternating with
fibrous or mucoid areas, with frequent hemorrhage and necrosis. Microscopically
it is composed of cells rich in lipids and glycogen, surrounded by an extensive
capillary network.Hypothesis
We
hypothesize that the biomechanical shear properties of renal tumors reflect the
underlying histological structure (including cellular distribution, vascular
architecture and extracellular-extravascular space) and therefore differ
between renal oncocytoma and RCC.Methods
Following
IRB approval, informed consent, and initial MRE optimization in 10 healthy
volunteers, 20 patients with renal tumors (up to 5 cm) scheduled for partial or
total nephrectomy were recruited prospectively. Imaging was performed on a 3T
MRI system (Biograph mMR, Siemens Healthcare, Erlangen, Germany) and included
anatomical T2 HASTE, DCE MRI (3D spoiled gradient echo; temporal resolution =
6.4 s; 34 measurements; Gadovist®; two-compartment Tofts model) and DWI (b =
50, 500, 800). Mechanical vibrations at
30Hz were transmitted from a mechanical transducer (Resoundant®)sited over the kidney of
interest. MRE was based upon a prototype 2D multi-slice interleaved gradient
echo sequence synchronized with the transducer's vibrations7: TE =
7.38 ms; motion encoding gradient amplitude = 30 mT/m; GRAPPA acceleration
factor = 2. Four consecutive breath-holds of 17 sec each (3 motion-encoding
directions and one reference scan) provided MRE data within 6 consecutive
slices of 128 x 88 pixels at 3 mm isotropic resolution and 4 wave phase
offsets. Reconstruction of viscoelastic parameters used firstly the application
of the curl operator for removal of the compressional component, secondly a
direct inversion of the Helmholtz equation8. Viscoelastic parametric
maps, including shear wave attenuation (α, mm-1) and velocity (C,
m/s) were generated offline on dedicated in-house software and regions of
interest (ROI) drawn around lesions. Median parametric values between the two
histologies were compared using the Wilcoxon rank-sum test. A screening model
using each independent imaging variable iteratively was applied to identify the
best classifier. Statistical significance was set at 5%.Results
One
dataset of insufficient MRE quality and one case of rare benign histology were excluded,
leaving 18 complete MR imaging datasets for analysis. Axial tumor diameters
ranged between 2.5 and 5.0 cm. MRE mechanical vibrations showed good unilateral
wave penetration (Figure 1). Histological assessment revealed 5 renal oncocytomas
(Figure 2) and 13 RCC (12 clear cell; 1 papillary type 1; Figure 3).
Shear wave
attenuation α was the only parameter showing significant differences between
the two histologies (P = 0.035), being higher in oncocytomas than in RCC: median (IQR) = 0.088 mm-1 (0.012) vs 0.062 mm-1 (0.036).
Shear
wave velocity C was closest to statistical significance (P = 0.075), being
lower in oncocytomas: 1.130 m/s (0.075)
vs 1.387 m/s (0.403).
Oncocytomas appeared overall more vascular than RCC, with
higher transfer and rate constants [Ktrans = 0.236 min-1 (0.216)
vs 0.166 min-1 (0.105); kep
= 0.657 min-1 (0.603) vs 0.512
min-1 (0.329); P = 0.173 and 0.246 respectively]. ADC and T2 signal intensity (SI) values were
not discriminatory (Figure 4), ADC ranging between 838.92 x 10-6 and 2482.76 x 10-6
mm2/s across tumors (P = 0.387).
MRE α and C proved to
be the strongest predictors of correct histology (Chi-squared P values = 0.015;
Figure 5), followed by DCE MRI Ktrans (P = 0.049).
Conclusion
Our
exploratory data suggests that biomechanical properties differ between renal
oncocytoma and RCC, with higher median attenuation (α) and lower median
velocity (C) in oncocytoma; α and C appear to be stronger discriminators than
biomarkers provided by DCE MRI, DWI or T2-weighted imaging. This shows
potential for clinical validation in a larger patient cohort.Acknowledgements
The
authors acknowledge financial support from the Royal College of Radiologists
through the Clinical Radiology Pump Priming Grant scheme; from the Department
of Health via the National Institute for Health Research Comprehensive
Biomedical Research Centre award to Guy’s and St Thomas’ NHS Foundation Trust,
in partnership with King’s College London and King’s College Hospital NHS
Foundation Trust; and from the King’s College London/University College London
Comprehensive Cancer Imaging Centre funded by Cancer Research UK and
Engineering and Physical Sciences Research Council, in association with the
Medical Research Council and Department of Health.References
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