Assessing mechanical properties of tissue biopsies to increase diagnosis accuracy

A novel needle-based piezoelectric device for guided tissue targeting enabled by mechanical sensing
Assessing mechanical properties of tissue biopsies to increase diagnosis accuracy

The paper in Nature Biomedical Engineering is here:

Research over the past several decades has uncovered the direct correlation between the mechanical properties of tissues and disease states, ranging from inflammation to fibrosis and cancer. Elastic modulus—the relationship between strain and stress—can serve as the basis for non-invasive medical diagnostics of soft tissues, especially the inner organs of the human body such as the liver, kidney, lung and brain. As normal tissue becomes afflicted with disease, including states of chronic inflammation or malignancy, the resulting changes in the elastic modulus can be used to locate and identify the dysfunction. Existing methods for physical characterization of tumors rely on bulk measurements of displacement (i.e. strain) as a function of an applied force (i.e. stress) delivered through vacuum suction, compression, or the nano-indentation of tissues, typically performed ex vivo. The associated tools are typically large, posing challenges for use in the direct evaluation of organ tissues in actual patients. Alternative approaches that rely only on minute deformations of the tissue could enable similar measurements of modulus in deployable, miniaturized forms of clinical relevance in an intraoperative setting.

Our lab began developing such methods for measuring soft tissue modulus using flexible devices in 20141. Considering the properties of chemistry, physics, mechanics, and biology of soft tissues, our task has been to select proper materials for sensing and actuation, and engineering these materials into biocompatible devices, in miniaturized forms. A piezoelectric material, called lead zirconate titanate (PZT) was selected as the basis for our sensors and actuators owing to its high sensitivity and great chemical/physical stability. The initial device, referred to as “Device 1”, is shown in Figure 1. The needle-shaped format includes a pair of separately addressable PZT membranes. With finite element analysis of the 3D mechanics of this system, integrated with experimental calibration by dynamic mechanical analysis, Device 1 can accurately sense the elastic modulus of soft tissue across a wide range relevant to biological organs from several kPa to MPa. This range covers the modulus values of all soft organ tissues, carrying a clear potential for clinically relevant applications. 

Figure 1. Tissue modulus probes based on ultrathin PZT actuators and sensors. a, Exploded-view schematic illustrations of Device 1 (free standing) and Device 2 (integrated on a biopsy needle). b, Optical images of Device 1. The inset shows an array of devices, and a magnified view of a sensor/actuator pair. c, Image of Device 1 placed on a biological tissue. d, Optical images of Device 2. The insets shows an image of Device 2 on a biological tissues. e, Magnified view of the sensor and actuator regions on the biopsy needle substrate. Figure adapted from ref.2; Macmillan Publishers.

As our research progressed, we identified improved embodiments, as shown in Device 2, which use a conventional steel biopsy needle as a platform to enable the penetration of skin, fascia and solid organs and positioning within a lesion for the assessment of organ pathology, diagnosis and/or to give treatment, shown in Figure 1. This idea emerged when Dr. Rahmi Oklu, Professor and Chair of interventional radiology at Mayo Clinic, Arizona, visited our lab at the University of Illinois at Urbana-Champaign for the first time. Working together with Dr. Oklu, we further developed the modulus sensor by adapting current biopsy needles with the PZT actuator and sensor.  In the era of personalized medicine, accurate tissue targeting for genomic studies is critical for diagnosis and for guiding clinical management. With current miss-rates as high as 20%, we aimed to equip biopsy needles with our sensor to increase accuracy of tissue targeting. Our results demonstrate the feasibility of detecting liver cancer in situations where false negative rates following percutaneous biopsies of small lesions are common, as shown in Figure 2. Moreover, the modulus values obtained from recipient livers determined by these platforms are consist with those obtained by the gold standard, magnetic resonance elastography techniques, further validating our technology.

Figure 2. Demonstration of modulus-based biopsy guidance in cancerous human tissue samples. a, Magnetic resonance electrographs (MRE) of the cirrhotic liver with tumor, presented as a two dimensional map of the shear modulus in a plane neared the center of the organ. b, Cross sectional schematic diagram of the sites for measurement using the modulus sensor probes. c, Modulus values measured from non-neoplastic and cancerous tissues using biopsy sensor device. Figure adapted from ref.2; Macmillan Publishers.

Our paper: Yu, X. et al. Needle-shaped ultrathin piezoelectric microsystem for guided tissue targeting via mechanical sensing. Nat. Biomed. Eng. (2018) doi:10.1038/s41551-018-0201-6.

1.Dagdeviren, C. et al. Conformal piezoelectric systems for clinical and experimental characterization of soft tissue biomechanics. Nat. Mater. 14, 728-736 (2015).
2.Yu, X. et al. Needle-shaped ultrathin piezoelectric microsystem for guided tissue targeting via mechanical sensing. Nat. Biomed. Eng. (2018).