Material characterization of ex vivo prostate tissue via spherical indentation in the clinic

Carson, William C.; Gerling, Gregory J.; Krupski, Tracey L.; Kowalik, Casey G.; Harper, Jeffrey C.; Moskaluk, Christopher A.

doi:10.1016/j.medengphy.2010.10.013

Cited by 49 publications

(41 citation statements)

References 25 publications

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“…This contrasts with the findings of many other groups who used large mechanical indenters at relatively higher frequencies for identification of prostate disease within prostates [16]–[18]. The decision to use a lower frequency came about from previous work from our group where we showed using lower frequency was better able to differentiate benign from malignant prostate tissue [14].…”

Section: Discussioncontrasting

confidence: 75%

Tissue Quality Assessment Using a Novel Direct Elasticity Assessment Device (The E-Finger): A Cadaveric Study of Prostatectomy Dissection

et al. 2014

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IntroductionMinimally invasive radical prostatectomy (RP) (robotic and laparoscopic), have brought improvements in the outcomes of RP due to improved views and increased degrees of freedom of surgical devices. Robotic and laparoscopic surgeries do not incorporate haptic feedback, which may result in complications secondary to inadequate tissue dissection (causing positive surgical margins, rhabdosphincter damage, etc). We developed a micro-engineered device (6 mm2 sized) [E-finger]) capable of quantitative elasticity assessment, with amplitude ratio, mean ratio and phase lag representing this. The aim was to assess the utility of the device in differentiating peri-prostatic tissue types in order to guide prostate dissection.Material and MethodsTwo embalmed and 2 fresh frozen cadavers were used in the study. Baseline elasticity values were assessed in bladder, prostate and rhabdosphincter of pre-dissected embalmed cadavers using the micro-engineered device. A measurement grid was created to span from the bladder, across the prostate and onto the rhabdosphincter of fresh frozen cadavers to enable a systematic quantitative elasticity assessment of the entire area by 2 independent assessors. Tissue was sectioned along each row of elasticity measurement points, and stained with haematoxylin and eosin (H&E). Image analysis was performed with Image Pro Premier to determine the histology at each measurement point.ResultsStatistically significant differences in elasticity were identified between bladder, prostate and sphincter in both embalmed and fresh frozen cadavers (p = <0.001). Intra-class correlation (ICC) reliability tests showed good reliability (average ICC = 0.851). Sensitivity and specificity for tissue identification was 77% and 70% respectively to a resolution of 6 mm2.ConclusionsThis cadaveric study has evaluated the ability of our elasticity assessment device to differentiate bladder, prostate and rhabdosphincter to a resolution of 6 mm2. The results provide useful data for which to continue to examine the use of elasticity assessment devices for tissue quality assessment with the aim of giving haptic feedback to surgeons performing complex surgery.

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Section: Discussioncontrasting

confidence: 75%

Tissue Quality Assessment Using a Novel Direct Elasticity Assessment Device (The E-Finger): A Cadaveric Study of Prostatectomy Dissection

et al. 2014

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“…13 This work confirmed that within a prostate, malignant tissue is consistently less elastic (more stiff) than healthy prostate tissue. However, although this ex vivo technique is robust scientifically, an in situ DRE has to contend with the anal sphincter, rectal wall and active blood flow.…”

Section: Introductionsupporting

confidence: 74%

“…Tissue with histological benign prostate hypertrophy had increased EM values (median 27.3 kPa) compared with normal tissue. 13 In this study, we went a step further and linked the different EM values to clinical exam findings and identified the association of EM with physical exam findings and with histopathologic findings. Seven of our initial cohort of 21 patients had a suspicious cue on DRE.…”

Section: Discussionmentioning

confidence: 99%

Construct validity in a high-fidelity prostate exam simulator

Kowalik

Gerling

Lee

et al. 2011

Prostate Cancer Prostatic Dis

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BACKGROUND: All health care practitioners should be facile in the digital rectal exam (DRE) as it provides prostate, rectal and neurological information. The purpose of this study was first to justify our hypothesis that tissue elasticity is indicative of carcinomatous changes. Second, we employed urological surgeons to evaluate our prostate simulator in three ways: (1) authenticate that the elasticity of the simulated prostates accurately represents the range of normal prostate stiffness, (2) determine the range of nodule size reasonably palpable by DRE and (3) discern what degree of elasticity difference within the same prostate suggests malignancy. METHODS:Institutional Review Board-approved materials characterization, human-subjects experiments, histopathology and chart abstraction of clinical history were performed. Material characterization of 21 ex-vivo prostatectomy specimens was evaluated using a custom-built, portable spherical indentation device while a novel prostate simulator was employed to measure human-subject perception of prostatic state. RESULTS:From the materials characterization, the measurements of the 21 gross prostates and 40 cross-sections yielded 306 data points. Within the same prostate, cancer was always stiffer. Of the seven cases with an abnormal DRE, the DRE accurately identified adenocarcinoma in 85%. From the human-subjects experiments, the simulated prostates evaluated by urologists ranged in stiffness from 8.9 to 91 kPa, mimicking the range found on ex vivo analysis of 4.6-236.7 kPa. The urological surgeons determined the upper limit of stiffness palpated as realistic for a healthy prostate was 59.63 kPa while the lower limit of stiffness was 27.1 kPa. Nodule size less than 7.5 mm was felt to be too small to reasonably palpate. CONCLUSIONS:We found it is not the absolute elasticity of the nodule, but rather the relationship of the nodule with the background prostate elasticity that constitutes the critical tactile feedback. Prostate simulator training may lead to greater familiarity with pertinent diagnostic cues and diagnosis of prostate cancer.

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“…Incubation with 50 mM GLA for 6 hr and 14 hr respectively increased the elastic moduli of the pure rBM gel to 175 ± 90 and 322 ± 160 compared to 122 ± 55 Pascals in rBM gels treated with PBS ( Table 1). This 1.7 to 3.2-fold increase in rBM stiffness recapitulates the 2.5-to 3.4-fold increase in stiffness observed in malignant compared to normal prostate or BPH tissue [23][24][25][26] . As outlined in a recent publication 13 the morphological changes induced by the accumulation of AGE and rBM stiffness in PEC acini can be quantified for a statistically significant shift from a rounded to polygonal shape, decreased luminal/total acinar area, and protruding cells migrating from the acina into the AGE-rich rBM (Figure 3).…”

supporting

confidence: 67%

How to Study Basement Membrane Stiffness as a Biophysical Trigger in Prostate Cancer and Other Age-related Pathologies or Metabolic Diseases

Rodriguez-Teja

Breit

Clarke

et al. 2016

JoVE

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Here we describe a protocol that can be used to study the biophysical microenvironment related to increased thickness and stiffness of the basement membrane (BM) during age-related pathologies and metabolic disorders (e.g. cancer, diabetes, microvascular disease, retinopathy, nephropathy and neuropathy). The premise of the model is non-enzymatic crosslinking of reconstituted BM (rBM) matrix by treatment with glycolaldehyde (GLA) to promote advanced glycation endproduct (AGE) generation via the Maillard reaction. Examples of laboratory techniques that can be used to confirm AGE generation, non-enzymatic crosslinking and increased stiffness in GLA treated rBM are outlined. These include preparation of native rBM (treated with phosphate-buffered saline, PBS) and stiff rBM (treated with GLA) for determination of: its AGE content by photometric analysis and immunofluorescent microscopy, its non-enzymatic crosslinking by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) as well as confocal microscopy, and its increased stiffness using rheometry. The procedure described here can be used to increase the rigidity (elastic moduli, E) of rBM up to 3.2-fold, consistent with measurements made in healthy versus diseased human prostate tissue. To recreate the biophysical microenvironment associated with the aging and diseased prostate gland three prostate cell types were introduced on to native rBM and stiff rBM: RWPE-1, prostate epithelial cells (PECs) derived from a normal prostate gland; BPH-1, PECs derived from a prostate gland affected by benign prostatic hyperplasia (BPH); and PC3, metastatic cells derived from a secondary bone tumor originating from prostate cancer. Multiple parameters can be measured, including the size, shape and invasive characteristics of the 3D glandular acini formed by RWPE-1 and BPH-1 on native versus stiff rBM, and average cell length, migratory velocity and persistence of cell movement of 3D spheroids formed by PC3 cells under the same conditions. Cell signaling pathways and the subcellular localization of proteins can also be assessed.

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Material characterization of ex vivo prostate tissue via spherical indentation in the clinic

Cited by 49 publications

References 25 publications

Tissue Quality Assessment Using a Novel Direct Elasticity Assessment Device (The E-Finger): A Cadaveric Study of Prostatectomy Dissection

Tissue Quality Assessment Using a Novel Direct Elasticity Assessment Device (The E-Finger): A Cadaveric Study of Prostatectomy Dissection

Construct validity in a high-fidelity prostate exam simulator

How to Study Basement Membrane Stiffness as a Biophysical Trigger in Prostate Cancer and Other Age-related Pathologies or Metabolic Diseases

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