Intraoperative probe for cancer diagnosis and treatment
An intraoperative probe combines Raman spectroscopy, shear wave elastography (SWE), and photodynamic therapy (PDT), preferably in a single hand-held device with real-time machine learning analysis. The machine learning independently analyzes and then fuses the data from different modalities for real-time cancer diagnostic predictions. The approach herein leverages simultaneous (or near-simultaneous) collection and real-time processing of Raman and SWE data for immediate cancer diagnostic feedback and therapeutic action. The hand-held device is precisely configured to target the same focal point with three different modalities—Raman, SWE, and PDT—by positioning the modalities within the device into the same location, either with an array of mirrors or an automatic or manual rotation mechanism.
1 . An intraoperative surgical probe for detecting and treating cancerous tissue in real-time, comprising:
a housing;
a motion tracking unit that receives one or more inputs, and in response continually generates tracking data representing a displacement of a focal region of tissue, and a predicted motion of the focal region over a given time horizon;
a first detection unit controllable to output a first output beam along a first axis, and in response receive first data;
a second detection unit controllable to output a second output beam along a second axis, and in response receive second data;
a treatment unit controllable to output a third output beam along a third axis
wherein the first, second and third axes are co-aligned so as to selectively converge one or more of the first, second and third output beams on the focal region of tissue; and
a control unit having a first portion, a second portion, and a third portion;
the first portion receiving and processing the tracking data to generate one or more output signals indicating that a residual motion of the focal region is less than a threshold;
the second portion responsive to a first output signal to activate the second detection unit in association with the first detection unit, to receive and analyze the first and the second data, generate respective first and second diagnostic outputs, and based on the first and second diagnostic outputs classify the tissue as normal or diseased; and
the third portion responsive to an indication from the second portion that the tissue is diseased together with receipt of a second output signal to arm the treatment unit to output the third output beam on the focal region of tissue.
2 . The intraoperative surgical probe as described in claim 1 , wherein the control unit includes a fourth portion, the fourth portion responsive to an activation of the treatment unit together with receipt of a third output signal to initiate a re-scan of the focal region of tissue.
3 . The intraoperative surgical probe as described in claim 1 , wherein the motion tracking unit comprises one or more sensors, wherein a sensor is one of: an ultrasound displacement sensor, an optical surface tracking sensor, an inertial measurement unit (IMU), an electromagnetic sensor, and a sensor responsive to one or more physiolic references.
4 . The intraoperative surgical probe as described in claim 3 , wherein the one or more physiolic references are one of: ECG-mid-diastole, and respiration.
5 . The intraoperative surgical probe as described in claim 1 , wherein the tracking data also includes a confidence level, and wherein an output signal of the one or more output signals is generated when the residual motion of the focal region is less than the threshold within the confidence level.
6 . The intraoperative surgical probe as described in claim 1 , wherein the first detection unit is a Shear Wave Elastography (SWE) unit, the first axis is an acoustic axis, the first output beam is an ultrasound beam, and the first data is data representing stiffness of the focal region of tissue.
7 . The intraoperative surgical probe as described in claim 1 , wherein the second detection unit is a Raman spectroscope, the second axis is an optical axis, the second output beam is scattered light, and the second data comprises Raman spectra.
8 . The intraoperative surgical probe as described in claim 1 , wherein the treatment unit is an ablation unit, the third axis is an optical axis, and the third output beam is coherent light.
9 . The intraoperative surgical probe as described in claim 8 , wherein the ablation unit destroys tissue and is one of: a cooled femtosecond pulsed laser, and a picosecond pulsed laser.
10 . The intraoperative surgical probe as described in claim 1 , wherein the treatment unit comprises a photodynamic therapy (PDT) subsystem configured to illuminate and thereby activate an administered photosensitizer at a therapeutically-effective wavelength to generate cytotoxic reactive species in the focal region.
11 . The intraoperative surgical probe as described in claim 1 , wherein the treatment unit comprises a photoimmunotherapy subsystem configured to illuminate and thereby activate an antibody-photosensitizer conjugate bound to target cells with near-infrared illumination to induce cell-selective phototoxicity in the focal region.
12 . The intraoperative surgical probe as described in claim 1 , wherein the given time horizon is in a range of 20-150 milliseconds.
13 . The intraoperative surgical probe as described in claim 1 , wherein the control unit second portion comprises a first machine learning model trained to classify the first data to produce the first diagnostic output, and a second machine learning model trained to classify the second data to produce the second diagnostic output.
14 . The intraoperative surgical probe as described in claim 13 , wherein the control unit second portion further comprises a third machine learning model trained to classify a fusion of first and second diagnostic outputs to produce an output prediction classifying the tissue as normal or diseased.
15 . The intraoperative surgical probe as described in claim 5 , wherein the confidence level is adjusted based on a prior diagnostic determination about the tissue, the prior diagnostic determination based on patient-specific data.
16 . The intraoperative surgical probe as described in claim 1 , further including a display supported in the housing on which an indication of the tissue as normal or diseased is rendered.
17 . The intraoperative surgical probe as described in claim 2 , wherein during the re-scan the first detection unit and the second detection unit are used to confirm absence of detectable residual disease.
18 . The intraoperative surgical probe as described in claim 7 , wherein the second detection unit is a wide-field Raman spectroscopy unit that provides multi-line Raman illumination and parallel detection of multiple Raman spectra.
19 . The intraoperative surgical probe as described in claim 1 , wherein the first detection unit operates according to a first modality, the second detection unit operates according to a second modality, and the treatment unit operates according to a third modality, wherein the first, second and third modalities differ from one another.
20 . The intraoperative surgical probe as described in claim 1 , wherein the housing is configured for one of: handheld support, and robotic support.
21 . The intraoperative surgical probe as described in claim 1 , wherein one of the first detection unit and the second detection unit are subjected to a compensation operation to cause the residual motion of the focal region to be less than the threshold.
22 . The intraoperative surgical probe as described in claim 21 , wherein the compensation operation is one of: beam steering, and micro-positioning.