Diagnostic accuracy of optical coherence tomography for surgical margin assessment of feline injection-site sarcoma.

The invasive, locally aggressive nature of feline injection-site sarcomas (FISSs) poses a unique challenge for surgeons to obtain complete margins with surgical excision. Optical coherence tomography (OCT), an imaging technology that uses light waves to generate real-time views of tissue architecture, provides an emerging solution to this dilemma by allowing fast, high-resolution scanning of surgical margins. The purpose of this study was to use OCT to assess surgical margins of FISS and to evaluate the diagnostic accuracy of OCT for detecting residual cancer using six evaluators of varying experience. Five FISSs were imaged with OCT to create a training set of OCT images that were compared with histopathology. Next, 25 FISSs were imaged with OCT prior to histopathology. Six evaluators of varying experience participated in a training session on OCT imaging after which each of the evaluators was given a dataset that included OCT images and videos to score on a scale from cancerous to non-cancerous. Diagnostic accuracy statistics were calculated. The overall sensitivity and specificity for classification of OCT images by evaluators were 78.9% and 77.6%, respectively. Correct classification rate of OCT images was associated with experience, while individual sensitivities and specificities had more variation between experience groups. This study demonstrates the ability of evaluators to correctly classify OCT images with overall low levels of experience and training and also illustrates areas where increased training can improve accuracy of evaluators in interpretation of OCT surgical margin images.

Biomechanical sensing of in vivo magnetic nanoparticle hyperthermia-treated melanoma using magnetomotive optical coherence elastography.

Rationale: Magnetic nanoparticle hyperthermia (MH) therapy is capable of thermally damaging tumor cells, yet a biomechanically-sensitive monitoring method for the applied thermal dosage has not been established. Biomechanical changes to tissue are known indicators for tumor diagnosis due to its association with the structural organization and composition of tissues at the cellular and molecular level. Here, by exploiting the theranostic functionality of magnetic nanoparticles (MNPs), we aim to explore the potential of using stiffness-based metrics that reveal the intrinsic biophysical changes of in vivo melanoma tumors after MH therapy. Methods: A total of 14 melanoma-bearing mice were intratumorally injected with dextran-coated MNPs, enabling MH treatment upon the application of an alternating magnetic field (AMF) at 64.7 kHz. The presence of the MNP heating sources was detected by magnetomotive optical coherence tomography (MM-OCT). For the first time, the elasticity alterations of the hyperthermia-treated, MNP-laden, in vivo tumors were also measured with magnetomotive optical coherence elastography (MM-OCE), based on the mechanical resonant frequency detected. To investigate the correlation between stiffness changes and the intrinsic biological changes, histopathology was performed on the excised tumor after the in vivo measurements. Results: Distinct shifts in mechanical resonant frequency were observed only in the MH-treated group, suggesting a heat-induced stiffness change in the melanoma tumor. Moreover, tumor cellularity, protein conformation, and temperature rise all play a role in tumor stiffness changes after MH treatment. With low cellularity, tumor softens after MH even with low temperature elevation. In contrast, with high cellularity, tumor softening occurs only with a low temperature rise, which is potentially due to protein unfolding, whereas tumor stiffening was seen with a higher temperature rise, likely due to protein denaturation. Conclusions: This study exploits the theranostic functionality of MNPs and investigates the MH-induced stiffness change on in vivo melanoma-bearing mice with MM-OCT and MM-OCE for the first time. It was discovered that the elasticity alteration of the melanoma tumor after MH treatment depends on both thermal dosage and the morphological features of the tumor. In summary, changes in tissue-level elasticity can potentially be a physically and physiologically meaningful metric and integrative therapeutic marker for MH treatment, while MM-OCE can be a suitable dosimetry technique.

Optical coherence tomography imaging of excised canine apocrine gland anal sac adenocarcinoma tumours.

Optical coherence tomography (OCT) is an optical imaging modality that has been investigated for real-time surgical margin evaluation in human breast cancer patients. Previous veterinary OCT studies have been limited to surgical margin imaging for soft tissue sarcoma (STS) tumours. To the authors knowledge, OCT has never been used to characterize or evaluate other types of neoplasia in dogs. The goal of this study was to characterize the OCT imaging appearance of apocrine gland anal sac adenocarcinoma (AGASACA) in excised ex vivo specimens from five client-owned dogs. All excised tissue surgical margins were imaged using a clinical spectral domain OCT system and two to four areas suspicious for incomplete surgical margins were selected. These areas were inked and sections were trimmed for histopathology. This enabled OCT imaging from each area of interest to be compared with corresponding H&E stained histology imaging from the same location. OCT was able to identify the presence of AGASACA at or within 1 mm of the surgical margin in all areas of interest. AGASACA, similar to the previously described canine STS, generated a dense, highly scattering image without any specific textural architecture. This study was able to validate the ability of OCT to accurately identify another type of tumour presence at or close to the surgical margin in the dog. Further study is needed to assess OCT accuracy at identifying other tumour types in dogs to understand its potential clinical applications.

The feasibility and utility of optical coherence tomography directed histopathology for surgical margin assessment of canine mast cell tumours.

Histopathologic surgical margin assessment in veterinary patients is an imprecise science with assessment limited to a small proportion of the surgical margin due to time and finances. Incomplete excision of canine mast cell tumours (MCTs) alters treatment recommendations and prognosis. Optical coherence tomography (OCT) is a novel imaging modality that has been reported in a single veterinary study for surgical margin assessment. Twenty-five dogs with 34 MCTs were enrolled in a prospective pilot-study to assess the imaging characteristics of canine MCTs with OCT and to evaluate the feasibility and utility of OCT-guided histopathology. All dogs underwent routine surgical excision of MCTs. OCT imaging was used to assess the entire surgical margin prior to placement in formalin. Either normal areas or areas suspected of incomplete MCT excision were inked. Standard histopathologic sectioning and tangential sectioning of inked areas were performed and compared to OCT results. OCT identified MCT near the surgical margin in 10 of 26 specimens (38.4%). Four specimens suspicious for incomplete margins on OCT had incomplete MCT excision that was missed on standard histopathologic sectioning. Six specimens had OCT-guided sections taken as suspicious, which did not show MCT on histopathology. OCT-guided pathology sections were able to detect incompletely excised MCT near the surgical margin with a sensitivity of 90% and specificity of 56.2% in this preliminary study. OCT imaging shows promise for guiding pathologists to areas of interest to improve the diagnostic accuracy of surgical margin assessment in excised canine MCTs.

Diagnostic accuracy of optical coherence tomography for assessing surgical margins of canine soft tissue sarcomas in observers of different specialties.

OBJECTIVE: To determine the diagnostic accuracy of optical coherence tomography (OCT) to assess surgical margins of canine soft tissue sarcoma (STS) and determine the influence of observer specialty and training. STUDY DESIGN: Blinded clinical prospective study. ANIMALS: Twenty-five dogs undergoing surgical excision of STS. METHODS: In vivo and ex vivo surgical margins were imaged with OCT after tumor resection. Representative images and videos were used to generate a training presentation and data sets. These were completed by 16 observers of four specialties (surgery, radiology, pathology, and OCT researchers). Images and videos from data sets were classified as cancerous or noncancerous. RESULTS: The overall sensitivity and specificity were 88.2% and 92.8%, respectively, for in vivo tissues and 82.5% and 93.3%, respectively, for ex vivo specimens. The overall accurate classification for all specimens was 91.4% in vivo and 89.5% ex vivo. There was no difference in accuracy of interpretation of OCT imaging by observers of different specialties or experience levels. CONCLUSION: Use of OCT to accurately assess surgical margins after STS excision was associated with a high sensitivity and specificity among various specialties. Personnel of all specialties and experience levels could effectively be trained to interpret OCT imaging. CLINICAL SIGNIFICANCE: Optical coherence tomography can be used by personnel of different specialty experience levels and from various specialties to accurately identify canine STS in vivo and ex vivo after a short training session. These encouraging results provide evidence to justify further research to assess the ability of OCT to provide real-time assessments of surgical margins and its applicability to other neoplasms.

Handheld optical coherence tomography for clinical assessment of dental plaque and gingiva.

SIGNIFICANCE: Optical coherence tomography (OCT) offers high spatial resolution and contrast for imaging intraoral structures, yet few studies have investigated its clinical feasibility for dental plaque and gingiva imaging in vivo. Furthermore, the accessibility is often limited to anterior teeth due to bulky imaging systems and probes. AIM: A custom-designed, handheld probe-based, spectral-domain OCT system with an interchangeable attachment was developed to assess dental plaque and gingival health in a clinical setting. APPROACH: Healthy volunteers and subjects with gingivitis and sufficient plaque were recruited. The handheld OCT system was operated by trained dental hygienists to acquire images of dental plaque and gingiva at various locations and after one-week use of oral hygiene products. RESULTS: The handheld OCT can access premolars, first molars, and lingual sides of teeth to visualize the plaque distribution. OCT intensity-based texture analysis revealed lower intensity from selected sites in subjects with gingivitis. The distribution of the dental plaque after one-week use of the oral hygiene products was compared, showing the capability of OCT as a longitudinal tracking tool. CONCLUSIONS: OCT has a strong potential to display and assess dental plaque and gingiva in a clinical setting. Meanwhile, technological challenges remain to perform systematic longitudinal tracking and comparative analyses.

Phase-based Eulerian motion magnification reveals eardrum mobility from pneumatic otoscopy without sealing the ear canal.

Pneumatic otoscopy is the recommended diagnostic method for middle ear infections. Physicians use a pneumatic otoscope to assess the position of the eardrum (bulging or retraction) as well as the eardrum mobility while an insufflation bulb is squeezed to generate air pressure changes in a sealed ear canal. While pneumatic otoscopy provides increased sensitivity and specificity by detecting decreased eardrum mobility, there exist many challenges to correctly perform and interpret results. For example, the ear canal must be sealed using a specialized ear speculum to deliver sufficiently large pressure changes that can induce visible movements of an eardrum. To overcome this challenge, video motion magnification is proposed to amplify pneumatic-induced motions of the eardrum without sealing of the ear canal. Pneumatic otoscopy is performed on adult subjects using a smartphone camera with an otoscope attachment at 60 frames per second, with pressure inputs at 5 Hz. Phase-based Eulerian motion magnification is applied to magnify spatiotemporal dependent motions in the video. As a result, the motion magnification of unsealed pneumatic otoscopy reveals comparable eardrum motions as in standard pneumatic otoscopy with a sealed ear canal. Furthermore, the estimated motions (in pixels) are quantified to examine the spatial and the temporal variations of the eardrum motions. The motion magnification may avoid the need for sealing the ear canal as well as decrease patient discomfort in pneumatic otoscopy, improving the capability and the usability as a point-of-care diagnostic tool in primary care and otology.

Single-shot two-dimensional spectroscopic magnetomotive optical coherence elastography with graphics processing unit acceleration.

Biomechanical contrast within tissues can be assessed based on the resonant frequency probed by spectroscopic magnetomotive optical coherence elastography (MM-OCE). However, to date, in vivo MM-OCE imaging has not been achieved, mainly due to the constraints on imaging speed. Previously, spatially-resolved spectroscopic contrast was achieved in a "multiple-excitation, multiple-acquisition" manner, where seconds of coil cooling time set between consecutive imaging frames lead to total acquisition times of tens of minutes. Here, we demonstrate an improved data acquisition speed by providing a single chirped force excitation prior to magnetomotion imaging with a BM-scan configuration. In addition, elastogram reconstruction was accelerated by exploiting the parallel computing capability of a graphics processing unit (GPU). The accelerated MM-OCE platform achieved data acquisition in 2.9 s and post-processing in 0.6 s for a 2048-frame BM-mode stack. In addition, the elasticity sensing functionality was validated on tissue-mimicking phantoms with high spatial resolution. For the first time, to the best of our knowledge, MM-OCE images were acquired from the skin of a living mouse, demonstrating its feasibility for in vivo imaging.

Assessing the Effect of Middle Ear Effusions on Wideband Acoustic Immittance Using Optical Coherence Tomography.

OBJECTIVES: Wideband acoustic immittance (WAI) noninvasively assesses middle ear function by measuring the sound conduction over a range of audible frequencies. Although several studies have shown the potential of WAI for detecting the presence of middle ear effusions (MEEs), determining the effects of MEE type and amount on WAI in vivo has been challenging due to the anatomical location of middle ear cavity. The purpose of this study is to correlate WAI measurements with physical characteristics of the middle ear and MEEs determined by optical coherence tomography (OCT), a noninvasive optical imaging technique. DESIGN: Sixteen pediatric subjects (average age of 7 ± 4 years) were recruited from the primary care clinic at Carle Foundation Hospital (Urbana, IL). A total of 22 ears (normal: 15 ears, otitis media with effusion: 6 ears, and acute otitis media: 1 ear, based on physician's diagnosis) were examined via standard otoscopy, tympanometry, OCT imaging, and WAI measurements in a busy, community-based clinical setting. Cross-sectional OCT images were analyzed to quantitatively assess the presence, type (relative turbidity based on the amount of scattering), and amount (relative fluid level) of MEEs. These OCT metrics were utilized to categorize subject ears into no MEE (control), biofilm without a MEE, serous-scant, serous-severe, mucoid-scant, and mucoid-severe MEE groups. The absorbance levels in each group were statistically evaluated at α = 0.05. RESULTS: The absorbance of the control group showed a similar trend when compared with a pediatric normative dataset, and the presence of an MEE generally decreased the power absorbance. The mucoid MEE group showed significantly less power absorbance from 2.74 to 4.73 kHz (p < 0.05) when compared with the serous MEE group, possibly due to the greater mass impeding the middle ear system. Similarly, the greater amount of middle ear fluid contributed to the lower power absorbance from 1.92 to 2.37 kHz (p< 0.05), when compared with smaller amounts of fluid. As expected, the MEEs with scant fluid only significantly affected the power absorbance at frequencies greater than 4.85 kHz. A large variance in the power absorbance was observed between 2 and 5 kHz, suggesting the dependence on both the type and amount of MEE. CONCLUSIONS: Physical characteristics of the middle ear and MEEs quantified from noninvasive OCT images can be helpful to understand abnormal WAI measurements. Mucoid MEEs decrease the power absorbance more than serous MEEs, and the greater amounts of MEE decreases the power absorbance, especially at higher (>2 kHz) frequencies. As both the type and amount of MEE can significantly affect WAI measurements, further investigations to correlate acoustic measurements with physical characteristics of middle ear conditions in vivo is needed.

Comparison between optical coherence tomographic and histopathologic appearances of artifacts caused by common surgical conditions and instrumentation.

OBJECTIVE: To document the appearance of artifacts created by commonly encountered surgical conditions and instrumentation on optical coherence tomography (OCT) and to compare these findings with histopathology. STUDY DESIGN: Ex vivo study. ANIMALS: Five canine cadavers. METHODS: Skin, subcutaneous fat, skeletal muscle, and fascia samples were obtained from fresh canine cadavers. Blood pooling, hemostatic crushing, scalpel blade cut, monopolar electrosurgery, bipolar vessel sealing device, and ultrasonic energy surgical artifacts were induced on each tissue type. Each specimen was imaged with OCT and subsequently histologically processed. RESULTS: Most surgical instrumentation used for tumor excision created a high-scattering region with local architectural disruption. Blood pooling was visible as a high-scattering layer overlying tissue with normal architecture. Only the scalpel blade created a focal, low-scattering area representing a sharply demarcated cut within the tissue distinct from the appearance of other instrumentation. CONCLUSION: Common surgical instruments and conditions encountered during tumor excision produced high-scattering OCT artifacts in tissues commonly seen at surgical margins. CLINICAL SIGNIFICANCE: The clinical value of OCT hinges on the ability of personnel to interpret this novel imaging and recognize artifacts. Defining and describing the appearance of common surgical artifacts provides a foundation to create image libraries with known histological and OCT interpretation, ultimately improving the diagnostic accuracy of OCT for assessment of surgical margins.

Characterization of Magnetic Nanoparticle-Seeded Microspheres for Magnetomotive and Multimodal Imaging.

Magnetic iron-oxide nanoparticles have been developed as contrast agents in magnetic resonance imaging (MRI) and as therapeutic agents in magnetic hyperthermia. They have also recently been demonstrated as contrast and elastography agents in magnetomotive optical coherence tomography and elastography (MM-OCT and MM-OCE, respectively). Protein-shell microspheres containing suspensions of these magnetic nanoparticles in lipid cores, and with functionalized outer shells for specific targeting, have also been demonstrated as efficient contrast agents for imaging modalities such as MM-OCT and MRI, and can be easily modified for other modalities such as ultrasound, fluorescence, and luminescence imaging. By leveraging the benefits of these various imaging modalities with the use of only a single agent, a magnetic microsphere, it becomes possible to use a widefield imaging method (such as MRI or small animal fluorescence imaging) to initially locate the agent, and then use MM-OCT to obtain dynamic contrast images with cellular level morphological resolution. In addition to multimodal contrast-enhanced imaging, these microspheres could serve as drug carriers for targeted delivery under image guidance. Although the preparation and surface modifications of protein microspheres containing iron oxide nanoparticles has been previously described and feasibility studies conducted, many questions regarding their production and properties remain. Since the use of multifunctional microspheres could have high clinical relevance, here we report a detailed characterization of their properties and behavior in different environments to highlight their versatility. The work presented here is an effort for the development and optimization of nanoparticle-based microspheres as multi-modal contrast agents that can bridge imaging modalities on different size scales, especially for their use in MM-OCT and MRI imaging.

Local wavefront mapping in tissue using computational adaptive optics OCT.

The identification and correction of wavefront aberrations is often necessary to achieve high-resolution optical images of biological tissues, as imperfections in the optical system and the tissue itself distort the imaging beam. Measuring the localized wavefront aberration provides information on where the beam is distorted and how severely. We have recently developed a method to estimate the single-pass wavefront aberrations from complex optical coherence tomography (OCT) data. Using this method, localized wavefront measurement and correction using computational OCT was performed in ex vivo tissues. The computationally measured wavefront varied throughout the imaged OCT volumes and, therefore, a local wavefront correction outperformed a global wavefront correction. The local wavefront measurement was also used to generate tissue aberration maps. Such aberration maps could potentially be used as a new form of tissue contrast.

Interstitial magnetic thermotherapy dosimetry based on shear wave magnetomotive optical coherence elastography.

While magnetic thermoseeds are often utilized in interstitial magnetic thermotherapy (iMT) to enable localized tumor ablation, we propose to extend their use as the perturbative source in magnetomotive optical coherence elastography (MM-OCE) so that the heat-induced elasticity alterations can be 'theranostically' probed. MM-OCE measurements were found to agree with indentation results. Tissue stiffening was visualized on iMT-treated porcine liver and canine soft tissue sarcoma specimens, where histology confirmed thermal damages. Additionally, the elasticity was found to increase exponentially and linearly with the conventional thermal dosage metrics and the deposited thermal energy, respectively. Collectively, a physiologically-meaningful, MM-OCE-based iMT dosimetry is feasible.

Effect of divalent ions and a polyphosphate on composition, structure, and stiffness of simulated drinking water biofilms.

The biofilm chemical and physical properties in engineered systems play an important role in governing pathogen transmission, fouling facilities, and corroding metal surfaces. Here, we investigated how simulated drinking water biofilm chemical composition, structure, and stiffness responded to the common scale control practice of adjusting divalent ions and adding polyphosphate. Magnetomotive optical coherence elastography (MM-OCE), a tool developed for diagnosing diseased tissues, was used to determine biofilm stiffness in this study. MM-OCE, together with atomic force microscopy (AFM), revealed that the biofilms developed from a drinking water source with high divalent ions were stiffer compared to biofilms developed either from the drinking water source with low divalent ions or the water containing a scale inhibitor (a polyphosphate). The higher stiffness of biofilms developed from the water containing high divalent ions was attributed to the high content of calcium carbonate, suggested by biofilm composition examination. In addition, by examining the biofilm structure using optical coherence tomography (OCT), the highest biofilm thickness was found for biofilms developed from the water containing the polyphosphate. Compared to the stiff biofilms developed from the water containing high divalent ions, the soft and thick biofilms developed from the water containing polyphosphate will be expected to have higher detachment under drinking water flow. This study suggested that water chemistry could be used to predict the biofilm properties and subsequently design the microbial safety control strategies.

Magnetomotive Displacement of the Tympanic Membrane Using Magnetic Nanoparticles: Toward Enhancement of Sound Perception.

OBJECTIVE: A novel hearing-aid scheme using magnetomotive nanoparticles (MNPs) as transducers in the tympanic membrane (TM) is proposed, aiming to noninvasively and directly induce a modulated vibration on the TM. METHODS: In this feasibility study, iron oxide (Fe3O4) nanoparticles were applied on ex vivo rat TM tissues and allowed to diffuse over ∼2 h. Subsequently, magnetic force was exerted on the MNP-laden TM via a programmable electromagnetic solenoid to induce the magnetomotion. Optical coherence tomography (OCT), along with its phase-sensitive measurement capabilities, was utilized to visualize and quantify the nanometer-scale vibrations generated on the TM tissues. RESULTS: The magnetomotive displacements induced on the TM were significantly greater than the baseline vibration of the TM without MNPs. In addition to a pure frequency tone, a chirped excitation and the corresponding spectroscopic response were also successfully generated and obtained. Finally, visualization of volumetric TM dynamics was achieved. CONCLUSION: This study demonstrates the effectiveness of magnetically inducing vibrations on TMs containing iron oxide nanoparticles, manipulating the amplitude and the frequency of the induced TM motions, and the capability of assessing the magnetomotive dynamics via OCT. SIGNIFICANCE: The results demonstrated here suggest the potential use of this noninvasive magnetomotive approach in future hearing aid applications. OCT can be utilized to investigate the magnetomotive dynamics of the TM, which may either enhance sound perception or magnetically induce the perception of sound without the need for acoustic speech signals.

Pneumatic low-coherence interferometry otoscope to quantify tympanic membrane mobility and middle ear pressure.

Pneumatic otoscopy to assess the mobility of the tympanic membrane (TM) is a highly recommended diagnostic method of otitis media (OM), a widespread middle ear infection characterized by the fluid accumulation in the middle ear. Nonetheless, limited depth perception and subjective interpretation of small TM displacements have challenged the appropriate and efficient examination of TM dynamics experienced during OM. In this paper, a pneumatic otoscope integrated with low coherence interferometry (LCI) was adapted with a controlled pressure-generating system to record the pneumatic response of the TM and to estimate middle ear pressure (MEP). Forty-two ears diagnosed as normal (n = 25), with OM (n = 10), or associated with an upper respiratory infection (URI) (n = 7) were imaged with a pneumatic LCI otoscope with an axial, transverse, and temporal resolution of 6 µm, 20 µm, and 1 msec, respectively. The TM displacement under pneumatic pressure transients (a duration of 0.5 sec with an intensity of ± 150 daPa) was measured to compute two metrics (compliance and amplitude ratio). These metrics were correlated with peak acoustic admittance and MEP from tympanometry and statistically compared via Welch's t-test. As a result, the compliance represents pneumatic TM mobility, and the amplitude ratio estimates MEP. The presence of a middle ear effusion (MEE) significantly decreased compliance (p<0.001). The amplitude ratio of the OM group was statistically less than that of the normal group (p<0.01), indicating positive MEP. Unlike tympanometry, pneumatic LCI otoscopy quantifies TM mobility as well as MEP regardless of MEE presence. With combined benefits of pneumatic otoscopy and tympanometry, pneumatic LCI otoscopy may provide new quantitative metrics for understanding TM dynamics and diagnosing OM.

Intraoperative optical coherence tomography of the human thyroid: Feasibility for surgical assessment.

Thyroid nodules assessed with ultrasound and fine-needle aspiration biopsy are diagnosed as "suspicious" or "indeterminate" in 15%-20% of the cases. Typically, total thyroidectomy is performed in such cases; however, only 25%-50% are found to be cancerous upon final histopathologic analysis. Here we demonstrate optical coherence tomography (OCT) imaging of the human thyroid as a potential intraoperative imaging tool for providing tissue assessment in real time during surgical procedures. Fresh excised tissue specimens from 28 patients undergoing thyroid surgery were imaged in the laboratory using a benchtop OCT system. Three-dimensional OCT images showed different microstructural features in normal, benign, and malignant thyroid tissues. A similar portable OCT system was then designed and constructed for use in the operating room, and intraoperative imaging of excised thyroid tissue from 6 patients was performed during the surgical procedure. The results demonstrate the potential of OCT to provide real-time imaging guidance during thyroid surgeries.

Quantitative characterization of mechanically indented in vivo human skin in adults and infants using optical coherence tomography.

Influenced by both the intrinsic viscoelasticity of the tissue constituents and the time-evolved redistribution of fluid within the tissue, the biomechanical response of skin can reflect not only localized pathology but also systemic physiology of an individual. While clinical diagnosis of skin pathologies typically relies on visual inspection and manual palpation, a more objective and quantitative approach for tissue characterization is highly desirable. Optical coherence tomography (OCT) is an interferometry-based imaging modality that enables in vivo assessment of cross-sectional tissue morphology with micron-scale resolution, which surpasses those of most standard clinical imaging tools, such as ultrasound imaging and magnetic resonance imaging. This pilot study investigates the feasibility of characterizing the biomechanical response of in vivo human skin using OCT. OCT-based quantitative metrics were developed and demonstrated on the human subject data, where a significant difference between deformed and nondeformed skin was revealed. Additionally, the quantified postindentation recovery results revealed differences between aged (adult) and young (infant) skin. These suggest that OCT has the potential to quantitatively assess the mechanically perturbed skin as well as distinguish different physiological conditions of the skin, such as changes with age or disease.

Magnetomotive Optical Coherence Elastography for Magnetic Hyperthermia Dosimetry Based on Dynamic Tissue Biomechanics.

Magnetic nanoparticles (MNPs) have been used in many diagnostic and therapeutic biomedical applications over the past few decades to enhance imaging contrast, steer drugs to targets, and treat tumors via hyperthermia. Optical coherence tomography (OCT) is an optical biomedical imaging modality that relies on the detection of backscattered light to generate high-resolution cross-sectional images of biological tissue. MNPs have been utilized as imaging contrast and perturbative mechanical agents in OCT in techniques called magnetomotive OCT (MM-OCT) and magnetomotive elastography (MM-OCE), respectively. MNPs have also been independently used for magnetic hyperthermia treatments, enabling therapeutic functions such as killing tumor cells. It is well known that the localized tissue heating during hyperthermia treatments result in a change in the biomechanical properties of the tissue. Therefore, we propose a novel dosimetric technique for hyperthermia treatment based on the viscoelasticity change detected by MM-OCE, further enabling the theranostic function of MNPs. In this paper, we first review the basic principles and applications of MM-OCT, MM-OCE, and magnetic hyperthermia, and present new preliminary results supporting the concept of MM-OCE-based hyperthermia dosimetry.

Mechanical contrast in spectroscopic magnetomotive optical coherence elastography.

The viscoelastic properties of tissues are altered during pathogenesis of numerous diseases and can therefore be a useful indicator of disease status and progression. Several elastography studies have utilized the mechanical frequency response and the resonance frequencies of tissue samples to characterize their mechanical properties. However, using the resonance frequency as a source of mechanical contrast in heterogeneous samples is complicated because it not only depends on the viscoelastic properties but also on the geometry and boundary conditions. In an elastography technique called magnetomotive optical coherence elastography (MM-OCE), the controlled movement of magnetic nanoparticles (MNPs) within the sample is used to obtain the mechanical properties. Previous demonstrations of MM-OCE have typically used point measurements in elastically homogeneous samples assuming a uniform concentration of MNPs. In this study, we evaluate the feasibility of generating MM-OCE elastograms in heterogeneous samples based on a spectroscopic approach which involves measuring the magnetomotive response at different excitation frequencies. Biological tissues and tissue-mimicking phantoms with two elastically distinct regions placed in side-by-side and bilayer configurations were used for the experiments, and finite element method simulations were used to validate the experimental results.