iPAT system technical improvements

The current iPAT system prototype embodies many desirable features of an ideal intraoperative specimen analyzer, including 3D volumetric visualization, multispectral capability, large FOV, and sensitivity to multiple lesion sub-types. However, the preceding theoretical and clinical discussion outlined further

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unmet needs, including surgical aid visualization, sub-millimeter margin measurements, wavelength selection range encompassing water and collagen spectral peaks, as well as decreased scan time and more user friendly specimen preparation and handling protocol. Here the technical improvements necessary to realize these capabilities are discussed.

5.3.1 Tissue illumination and imaging artefacts

In summary, the current iPAT system illumination employs an Nd-YAG laser coupled to an optical parametric oscillator (OPO) capable of generating output wavelengths in the 670 nm to 950 nm range, with energies up to 40 mJ/pulse and a repetition rate of 20 Hz. To expand the wavelength tuning range and enable efficient excitation of collagen and water, a laser with an OPO that tunes farther into the NIR should be employed, along with fiber optics featuring the appropriate spectral transmission range. For example, one group utilized a laser able to generate output from 670 nm to 2300 nm20.

In terms of illumination geometry, currently, the laser system directs a 3 cm diameter light beam along a single vertical line of sight, perpendicularly to the largest plane intersecting the compressively flattened specimen. Due to this unidimensional illumination, shadows are cast below highly absorbing features, as well as areas presenting a steep incline to the laser beam, such as near the outer edges of the specimen. While light diffusion in deep tissue typically smoothens out any steep illumination gradients, the surface and sub-surface regions remain vulnerable. To mitigate the shadowing artefact problem, the illumination scheme should be modified to ideally come from multiple directions, similarly to the employed hemispherical signal detection geometry. This would reduce the dependence of the incident laser fluence on one particular angle, hence maintaining a more homogeneous fluence overall.

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5.3.2 PA signal detection and scan speed

As previously described, at the heart of the iPAT system is a unique 24-channel acoustic transducer array, featuring highly sensitive wide-band polymer (PVDF) transducer elements with a low sub-MHz peak frequency. This detection scheme is favourable due to its exquisite sensitivity to bulk tissue, enabling visualization of large centimeter-level features, including tumours. However, the use of transducers of a single low-frequency limits the attainable resolution, and in fact, reduces the sensitivity, and ultimately detectability, of signals originating from millimeter and sub-millimeter features, such as surgical aides and vasculature.

Accordingly, redesigning the iPAT transducer array should include use of multiple transducer types to enable the detection of small imaging targets and to increase the attainable imaging resolution. Due to their reasonable compromise between ease of fabrication, sensitivity, and acoustic impedance match to tissue, some groups have begun employing transducer elements with composite piezoelectric materials7. Other groups have resorted to using conventional piezoelectric ceramics, such as PZT, due to their excellent sensitivity and widespread availability19. These options should be investigated for iPAT array fabrication, however, the resonant properties of these materials may be ill-suited to the detection of transient PA waves in water and tissue. Alternatively, our group has previously reported on use of various PVDF co-polymer materials and PA transducer construction methods, demonstrating excellent acoustic impedance match to tissue, high sensitivity, and sub-millimeter resolution4,5,21. Logically, these expertise should be applied to the design and construction of a multi-frequency iPAT transducer array.

To capture a full hemisphere of projection measurements, necessary for high quality PA image reconstruction, the current iPAT scanner spends a majority of time rotating the 24-element arc-shaped transducer array. Therefore, designing a new array with more elements would be a straight-forward way to increase the scan speed. For example, a hemispherical staring transducer array, utilizing 240-elements, would eliminate the need for rotational scan motion, and would potentially reduce scan time from 6

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minutes to just 40 seconds. Our group has previously published results demonstrating the capabilities of a staring 128-channel hemispherical PA array, consequently, an array with 240-channels implies a relatively simple extension of existing technology4.

5.3.3 Sample immobilization

To prepare a fresh lumpectomy for scanning in the iPAT system requires placement of the specimen inside a customized saline-filled Ziploc bag, drainage of excess saline, installation of the sealed and drained bag onto the lumpectomy holder, and insertion of the holder into the iPAT system’s water tank. Furthermore, if air bubbles infiltrate the bag or are unintentionally overlooked, the process must be repeated to minimize risk of imaging artefacts. In our experience, this sub-optimal procedure represents one of the best opportunities for improvement, particularly in specimen processing time. There are a number of possible approaches to enable a faster and smoother specimen handling experience. Ideally, a mechanized instrument should be designed that would accept a suture oriented specimen of arbitrary shape. The instrument should be capable of automatically processing, positioning, inverting and finally ejecting the specimen. This could be realized by use of a simple water-proof translation stage, coupled to a modified version of a commercially available vacuum sealer. Alternatively, a simpler design could be implemented by separating the specimen processing task from the specimen-holder insertion task.