The role of functional imaging in the era of targeted therapy of renal cell carcinoma

Braunagel, Margarita; Graser, Anno; Reiser, Maximilian; Notohamiprodjo, Mike

doi:10.1007/s00345-013-1074-7

Cited by 18 publications

(8 citation statements)

References 75 publications

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“…Morphological imaging modalities such as ultrasonography, computed tomography and magnetic resonance imaging are not ideally suited for detection of renal parenchymal disease, as early changes rather affect the ultrastructure and function than gross morphology [6] . Functional techniques such as perfusion and diffusion weighted MR imaging may reveal microstructural and functional changes [7] – [9] , but spatial resolution is low [10] , acquisition is not standardized and analysis is heavily influenced by the post-processing method [11] .…”

Section: Introductionmentioning

confidence: 99%

X-Ray Phase-Contrast Tomography of Renal Ischemia-Reperfusion Damage

Velroyen¹,

Bech

Zanette³

et al. 2014

PLoS ONE

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PurposeThe aim of the study was to investigate microstructural changes occurring in unilateral renal ischemia-reperfusion injury in a murine animal model using synchrotron radiation.Material and MethodsThe effects of renal ischemia-reperfusion were investigated in a murine animal model of unilateral ischemia. Kidney samples were harvested on day 18. Grating-Based Phase-Contrast Imaging (GB-PCI) of the paraffin-embedded kidney samples was performed at a Synchrotron Radiation Facility (beam energy of 19 keV). To obtain phase information, a two-grating Talbot interferometer was used applying the phase stepping technique. The imaging system provided an effective pixel size of 7.5 µm. The resulting attenuation and differential phase projections were tomographically reconstructed using filtered back-projection. Semi-automated segmentation and volumetry and correlation to histopathology were performed.ResultsGB-PCI provided good discrimination of the cortex, outer and inner medulla in non-ischemic control kidneys. Post-ischemic kidneys showed a reduced compartmental differentiation, particularly of the outer stripe of the outer medulla, which could not be differentiated from the inner stripe. Compared to the contralateral kidney, after ischemia a volume loss was detected, while the inner medulla mainly retained its volume (ratio 0.94). Post-ischemic kidneys exhibited severe tissue damage as evidenced by tubular atrophy and dilatation, moderate inflammatory infiltration, loss of brush borders and tubular protein cylinders.ConclusionIn conclusion GB-PCI with synchrotron radiation allows for non-destructive microstructural assessment of parenchymal kidney disease and vessel architecture. If translation to lab-based approaches generates sufficient density resolution, and with a time-optimized image analysis protocol, GB-PCI may ultimately serve as a non-invasive, non-enhanced alternative for imaging of pathological changes of the kidney.

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Section: Introductionmentioning

confidence: 99%

X-Ray Phase-Contrast Tomography of Renal Ischemia-Reperfusion Damage

Velroyen¹,

Bech

Zanette³

et al. 2014

PLoS ONE

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“…The fused PET/MR technology has further improved the assessment of soft-tissue for diagnostic purposes(11, 12). Functional imaging using PET has previously been evaluated in ccRCC to predict and evaluate response to systemic treatment(13, 14), but such studies have been challenged by the variable uptake of glucose in these tumors. Not surprisingly, this methodology has yet to be adopted into general practice for screening or disease assessment(15, 16).…”

Section: Resultsmentioning

confidence: 99%

Alternate Metabolic Programs Define Regional Variation of Relevant Biological Features in Renal Cell Carcinoma Progression

Brooks

Khandani

Lin

et al. 2016

Clinical Cancer Research

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Purpose: Clear cell renal cell carcinoma (ccRCC) has recently been redefined as a highly heterogeneous disease. In addition to genetic heterogeneity, the tumor displays risk variability for developing metastatic disease, therefore underscoring the urgent need for tissue-based prognostic strategies applicable to the clinical setting. We have recently employed the novel PET/magnetic resonance (MR) image modality to enrich our understanding of how tumor heterogeneity can relate to gene expression and tumor biology to assist in defining individualized treatment plans.Experimental Design: ccRCC patients underwent PET/MR imaging, and these images subsequently used to identify areas of varied intensity for sampling. Samples from 8 patients were subjected to histologic, immunohistochemical, and microarray analysis.Results: Tumor subsamples displayed a range of heterogeneity for common features of hypoxia-inducible factor expression and microvessel density, as well as for features closely linked to metabolic processes, such as GLUT1 and FBP1. In addition, gene signatures linked with disease risk (ccA and ccB) also demonstrated variable heterogeneity, with most tumors displaying a dominant panel of features across the sampled regions. Intriguingly, the ccA-and ccB-classified samples corresponded with metabolic features and functional imaging levels. These correlations further linked a variety of metabolic pathways (i.e., the pentose phosphate and mTOR pathways) with the more aggressive, and glucose avid ccB subtype.Conclusions: Higher tumor dependency on exogenous glucose accompanies the development of features associated with the poor risk ccB subgroup. Linking these panels of features may provide the opportunity to create functional maps to enable enhanced visualization of the heterogeneous biologic processes of an individual's disease.

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“…Therefore, in 2012, Ignee et al [8] first considered CEUS as the method of choice for all patients with impaired renal function in detecting RCC, using nonnephrotoxic, highly echogenic microbubbles that are able to enter the microcirculation and allow for real-time assessment of the arterial phase and vascular enhancement in RCC [13]. CEUS is minimally invasive, easy to use, cheap, and allows for reproducible measurements without adverse effects [14]. Papillary RCC seems to be the most predominant histological subtype in acquired cystic kidney disease-associated RCC in native kidneys (up to 70% compared to 10-15% in sporadic RCC) [15] but occurs also in transplanted kidneys [5,8,11], with unique described features on contrast-enhanced imaging as following: papillary RCC has less intratumoral vascularity and enhances less than clear-cell RCC in all phases of contrast-enhanced imaging [16].…”

Section: Discussionmentioning

confidence: 99%

De novo Renal Cell Carcinoma in a Kidney Allograft with Focus on Contrast-Enhanced Ultrasound

Pichler¹,

Heidegger²,

Bösmüller³

et al. 2014

Urol Int

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The development of de novo renal cell carcinoma (RCC) in a transplanted kidney is a rare condition. Currently, this is the second case report of a 41-year-old man in whom carcinoma of a renal allograft was detected by contrast-enhanced ultrasound (CEUS). An abdominal CT scan was not conclusive enough to differentiate between septal enhancement of a cyst and a low vascularized tumor. CEUS confirmed a solid, homogeneously enhancing but hypoechoic and hypovascular lesion compared to the surrounding kidney parenchyma without septal enhancement. Therefore, the patient underwent nephron-sparing surgery (NSS), affirming papillary RCC type 2. Graft function remained unchanged postoperatively; 12 months after NSS, no local recurrence or distant metastasis was described. CEUS seems to be a minimally invasive and efficient imaging option if other diagnostic tools cannot clearly exclude RCC, with the advantage of wide-ranging use, especially in cases of impaired renal function.

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The role of functional imaging in the era of targeted therapy of renal cell carcinoma

Cited by 18 publications

References 75 publications

X-Ray Phase-Contrast Tomography of Renal Ischemia-Reperfusion Damage

X-Ray Phase-Contrast Tomography of Renal Ischemia-Reperfusion Damage

Alternate Metabolic Programs Define Regional Variation of Relevant Biological Features in Renal Cell Carcinoma Progression

De novo Renal Cell Carcinoma in a Kidney Allograft with Focus on Contrast-Enhanced Ultrasound

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