Davide Prezzi1, Radhouene Neji2, James Stirling1, Sami Jeljeli1, Hema Verma3, Tim O'Brien4, Ben Challacombe4, Ashish Chandra5, Vicky Goh1, and Ralph Sinkus1
1Division of Imaging Sciences and Biomedical Engineering, King's College London, London, United Kingdom, 2MR Research Collaborations, Siemens Healthcare, Frimley, United Kingdom, 3Department of Radiology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom, 4Urology Centre, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom, 5Department of Histopathology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
Synopsis
Incidentally detected renal tumors are overtreated surgically, as up to 15% of them are benign, most frequently oncocytomas. We hypothesize that integrating
biomechanical with morphological MRI assessment can improve lesion
characterization, precluding unnecessary surgery. Initial experience and
pathological correlation in four resected renal oncocytomas and renal cell
carcinomas (RCC) demonstrate that 30Hz MRE with shear modulus elastography
parametric mapping is feasible, correlating spatially with gross pathology, with
lower viscosity/elasticity (y) ratios [mean = 0.22] in malignant RCCs compared
to oncocytomas [mean = 0.46], showing promise for clinical application.Purpose
·
To assess the feasibility of 3T
Magnetic Resonance Elastography (MRE) for evaluating renal tumors with
surgical pathology as the gold standard
·
To correlate the distribution
of MRI shear modulus elastography maps to same-level MRI anatomical sequences
including high-resolution HASTE and post contrast VIBE.
·
To correlate the distribution
of MRI shear modulus elastography maps to gross pathological morphology:
cellular distribution, vascular architecture and areas of necrosis to determine
how the underlying architecture affects biomechanical properties.
Background
With the growing use of cross-sectional imaging, the incidence of incidental
asymptomatic small renal tumors (≤ 4 cm) has risen
steadily [1, 2]. Although most of these lesions represent renal cell carcinoma
(RCC), up to 20% will be benign [3]. A recent estimate suggests that more than
5600 benign renal tumors are resected yearly in the United States [4]. Renal oncocytoma is the most common benign lesion, accounting for up
to 15% of all renal tumors, and cannot be differentiated from RCC reliably by
conventional imaging [5, 6]. On gross pathology oncocytomas have a
characteristic macroscopic appearance of homogenous dark brown lesions with a
frequent central scar and absence of necrosis. Microscopically they consist of
tight cellular nests surrounded by myxoid or hyalinized stroma. Conversely,
clear cell RCCs, the most common subtype, consist of soft yellow material alternating
with fibrous or mucoid areas, and are frequently hemorrhagic and necrotic. Microscopically
they are composed of clear cells, rich in lipids and glycogen, surrounded by an
extensive capillary network.
Hypothesis
We hypothesize that renal tumor MRE
biomechanical properties are determined by the underlying tumor architecture,
including their cellular distribution, vascular architecture and nature of the
extracellular-extravascular space.
Methods
Following IRB approval, informed consent,
and initial MRE optimization in 5 healthy volunteers, 5 patients with renal
tumors (≤ 4 cm) scheduled for partial or total nephrectomy were recruited prospectively.
In addition to standard MRI (T2 HASTE, DWI and post contrast T1 VIBE), MRE was performed on
a 3T MRI system (Biograph mMR, Siemens Healthcare, Erlangen, Germany) based
upon a prototype 2D multi-slice interleaved gradient echo sequence synchronized with the transducer's vibrations, TE = 7.38 ms, motion encoding gradient amplitude = 30 mT/m and GRAPPA acceleration factor = 2 [7]. Mechanical vibrations at 30Hz were
transmitted from the mechanical transducer sited over the kidney
of interest. 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 an iterative
method comparing the measured with the simulated curl-field within a subzone of
11 x 11 x 5 pixels using the data as boundary condition on the surface of the
subzone (similar to [8]). Viscoelastic
parametric maps, including storage modulus (elasticity, kPa) and viscosity/elasticity
ratio [y=2/π*atan(Gl/Gd)] were generated and regions of interest (ROI) drawn around tumors.
Results
One patient was unable to tolerate the MRI.
Four MRI datasets, including MRE, were successfully acquired. Mechanical vibrations
showed good unilateral wave penetration (image 1). Histological assessment
revealed 2 renal oncocytomas (images 2 and 3) and 2 clear cell RCC (images 4
and 5). The two oncocytomas showed homogeneous intermediate T2 HASTE signal
with central hyperintensity and homogeneous contrast enhancement on T1 VIBE. RCCs
showed spatially heterogeneous T2 HASTE signal and T1 VIBE contrast
enhancement.
Mean ADC and Minimum ADC values were not obviously discriminatory, ranging between 1258.16 - 1823.29 x 10-6 mm2/s and 381.00 - 861.00 x 10-6 mm2/s respectively across tumors. Areas of necrosis and the central scar were excluded from MRE analysis. Mean elasticities were 1.14 and 2.50 kPa; y ratios were 0.52 and 0.40
for each oncocytoma respectively. Mean elasticities for each RCCs were higher
at 3.50 and 3.60 kPa; corresponding y ratios were lower at 0.3 and 0.15 kPa respectively.
Conclusion
Our initial exploratory data suggests that the
biomechanical properties differ between clear RCC and oncocytoma, with higher mean
elasticity and lower viscosity/elasticity ratios in RCCs, raising its potential
for clinical application. Ongoing prospective recruitment with pathological
correlation will provide confirmatory evidence.
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
1.
Hollingsworth JM, Miller DC,
Daignault S, et al. Rising incidence of small renal masses: a need to reassess
treatment effect. J Natl Cancer Inst. 2006; 98: 1331–1334.
2.
Gill IS, Aron M, Gervais DA, et
al. Clinical practice. Small renal mass. N Engl J Med. 2010; 362: 624–634.
3.
Frank
I, Blue ML, Cheville JC, et al. Solid renal tumors: an
analysis of pathological features related to tumor size. J Urol. 2003; 170:
2217–2220.
4.
Johnson DC, Vukina J, Smith AB,
et al. Preoperatively misclassified, surgically removed benign renal masses: a
systematic review of surgical series and United States population-level burden
estimate. J Urol. 2015; 193: 30–35.
5.
Pierorazio
PM, Hyams ES, Tsai S, et al. Multiphasic enhancement
patterns of small renal masses (<=4 cm) on preoperative computed tomography:
utility for distinguishing subtypes of renal cell carcinoma, angiomyolipoma,
and oncoctyoma. Urology. 2013; 81: 1265–1271.
6.
Pedrosa I, Sun MR, Spencer M,
et al. MR imaging of renal masses: correlation with findings at surgery and
pathologic analysis. Radiographics. 2008; 28: 985–1003.
7.
Garteiser
P, Sahebjavaher RS, Ter Beek LC et al. Rapid
acquisition of multifrequency, multislice and multidirectional MR elastography
data with a fractionally encoded gradient echo sequence. NMR Biomed. 2013;
26(10): 1326-1335.
8.
Van
Houten EE, Miga MI, Weaver JB et al. Three-dimensional
subzone-based reconstruction algorithm for MR elastography." Magn Reson
Med. 2001; 45(5): 827-837.