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Dynamic Diffuse Optical Tomography for Monitoring Neoadjuvant Chemotherapy in Patients with Breast Cancer

Gunther, Jacqueline E; Lim, Emerson A; Kim, Hyun K; Flexman, Molly; Altoé, Mirella; Campbell, Jessica A; Hibshoosh, Hanina; Crew, Katherine D; Kalinsky, Kevin; Hershman, Dawn L; Hielscher, Andreas H
Purpose To identify dynamic optical imaging features that associate with the degree of pathologic response in patients with breast cancer during neoadjuvant chemotherapy (NAC). Materials and Methods Of 40 patients with breast cancer who participated in a longitudinal study between June 2011 and March 2016, 34 completed the study. There were 13 patients who obtained a pathologic complete response (pCR) and 21 patients who did not obtain a pCR. Imaging data from six subjects were excluded from the study because either the patients dropped out of the study before it was finished or there was an instrumentation malfunction. Two weeks into the treatment regimen, three-dimensional images of both breasts during a breath hold were acquired by using dynamic diffuse optical tomography. Features from the breath-hold traces were used to distinguish between response groups. Receiver operating characteristic (ROC) curves and sensitivity analysis were used to determine the degree of association with 5-month treatment outcome. Results An ROC curve analysis showed that this method could identify patients with a pCR with a positive predictive value of 70.6% (12 of 17), a negative predictive value of 94.1% (16 of 17), a sensitivity of 92.3% (12 of 13), a specificity of 76.2% (16 of 21), and an area under the ROC curve of 0.85. Conclusion Several dynamic optical imaging features obtained within 2 weeks of NAC initiation were identified that showed statistically significant differences between patients with pCR and patients without pCR as determined 5 months after treatment initiation. If confirmed in a larger cohort prospective study, these dynamic imaging features may be used to predict treatment outcome as early as 2 weeks after treatment initiation. © RSNA, 2018 Online supplemental material is available for this article.
PMCID:5978455
PMID: 29431574
ISSN: 1527-1315
CID: 5389812

Assessment of Infantile Hemangiomas Using a Handheld Wireless Diffuse Optical Spectroscopic Device

Fong, Christopher J; Garzon, Maria C; Hoi, Jennifer W; Kim, Hyun K; Lauren, Christine T; Morel, Kimberly; Geller, Lauren; Antonov, Nina; Weitz, Nicole; Wu, June; Hielscher, Andreas H
BACKGROUND/OBJECTIVES/OBJECTIVE:Infantile hemangiomas (IHs) are vascular tumors with the potential for significant morbidity. There is a lack of validated objective tools to assess IH severity and response to treatment. Diffuse optical spectroscopy (DOS), a noninvasive, nonionizing imaging modality, can measure total hemoglobin concentration and hemoglobin oxygen saturation in tissue to assess IH vascularity and response to treatment. Our objective was to evaluate the utility of a wireless, handheld DOS system to assess IH characteristics at selected points during their clinical course. METHODS:Thirteen subjects (initial age 5.8 ± 2.0 mos) with 15 IHs were enrolled. IHs were classified as proliferative, plateau phase, or involuting. Nine patients with 11 IHs were untreated; four patients with 4 IHs were treated with timolol or propranolol. Each IH was evaluated by placing the DOS system directly on the lesion as well a normal contralateral skin site. IH vascularity and oxygenation were scored using a newly defined normalized hypoxia fraction (NHF) coefficient. Measurements were recorded at various intervals from the initial visit to 1 to 2 years of age. RESULTS:For the nine untreated IHs, the NHF was highest at 6 months of age, during proliferation. Differences in NHFs between the proliferation and the plateau (p = 0.02) and involuting (p < 0.001) stages were statistically significant. In treated patients, the NHF normalized to 60% after 2 months. One treated IH came within 5% of the NHF for normal skin after 12 months. CONCLUSIONS:DOS can be used to assess the vascularity and tissue oxygenation of IHs and monitor their progression and response to treatment.
PMCID:5501760
PMID: 28548465
ISSN: 1525-1470
CID: 5390032

Frequency-domain optical tomographic image reconstruction algorithm with the simplified spherical harmonics (SP3) light propagation model

Kim, Hyun Keol; Montejo, Ludguier D; Jia, Jingfei; Hielscher, Andreas H
We introduce here the finite volume formulation of the frequency-domain simplified spherical harmonics model with n-th order absorption coefficients (FD-SPN) that approximates the frequency-domain equation of radiative transfer (FD-ERT). We then present the FD-SPN based reconstruction algorithm that recovers absorption and scattering coefficients in biological tissue. The FD-SPN model with 3rd order absorption coefficient (i.e., FD-SP3) is used as a forward model to solve the inverse problem. The FD-SP3 is discretized with a node-centered finite volume scheme and solved with a restarted generalized minimum residual (GMRES) algorithm. The absorption and scattering coefficients are retrieved using a limited-memory Broyden-Fletcher-Goldfarb-Shanno (L-BFGS) algorithm. Finally, the forward and inverse algorithms are evaluated using numerical phantoms with optical properties and size that mimic small-volume tissue such as finger joints and small animals. The forward results show that the FD-SP3 model approximates the FD-ERT (S12) solution within relatively high accuracy; the average error in the phase (<3.7%) and the amplitude (<7.1%) of the partial current at the boundary are reported. From the inverse results we find that the absorption and scattering coefficient maps are more accurately reconstructed with the SP3 model than those with the SP1 model. Therefore, this work shows that the FD-SP3 is an efficient model for optical tomographic imaging of small-volume media with non-diffuse properties both in terms of computational time and accuracy as it requires significantly lower CPU time than the FD-ERT (S12) and also it is more accurate than the FD-SP1.
PMCID:5649649
PMID: 29062243
ISSN: 1290-0729
CID: 5390042

Diffuse optical tomography changes correlate with residual cancer burden after neoadjuvant chemotherapy in breast cancer patients

Lim, Emerson A; Gunther, Jacqueline E; Kim, Hyun K; Flexman, Molly; Hibshoosh, Hanina; Crew, Katherine; Taback, Bret; Campbell, Jessica; Kalinsky, Kevin; Hielscher, Andreas; Hershman, Dawn L
PURPOSE:Breast cancer (BC) patients who achieve a favorable residual cancer burden (RCB) after neoadjuvant chemotherapy (NACT) have an improved recurrence-free survival. Those who have an unfavorable RCB will have gone through months of ineffective chemotherapy. No ideal method exists to predict a favorable RCB early during NACT. Diffuse optical tomography (DOT) is a novel imaging modality that uses near-infrared light to assess hemoglobin concentrations within breast tumors. We hypothesized that the 2-week percent change in DOT-measured hemoglobin concentrations would associate with RCB. METHODS:We conducted an observational study of 40 women with stage II-IIIC BC who received standard NACT. DOT imaging was performed at baseline and 2 weeks after treatment initiation. We evaluated the associations between the RCB index (continuous measure), class (categorical 0, I, II, III), and response (RCB class 0/I = favorable, RCB class II/III = unfavorable) with changes in DOT-measured hemoglobin concentrations. RESULTS:] (p ≤ 0.01) and [HbT] (p ≤ 0.02). [HbT] 2-week percent change had sensitivity, specificity, positive, and negative predictive values for a favorable RCB response of 86.7, 68.4, 68.4, and 86.7%, respectively. CONCLUSION:The 2-week percent change in DOT-measured hemoglobin concentrations was associated with the RCB index, class, and response. DOT may help guide NACT for women with BC.
PMCID:9434699
PMID: 28190249
ISSN: 1573-7217
CID: 5390022

Diffuse optical tomography can predict pathologic complete response in patients with HER2+or triple negative breast cancer undergoing neoadjuvant chemotherapy [Meeting Abstract]

Kalinsky, K.; Lee, S.; Zhong, X.; Lim, E. A.; Gunther, J. E.; Hibshoosh, H.; Kim, H. K.; Accordino, M.; Crew, K.; Hielscher, A.; Hershman, D. L.
ISI:000397999001257
ISSN: 0008-5472
CID: 5390392

Baseline oxygen saturation comparison between pathologic complete responders and extensive residual cancer cases in response to neoadjuvant chemotherapy [Meeting Abstract]

Altoe, Mirella L.; Gunther, Jacqueline E.; Lim, Emerson; Kim, Hyun Keol; Campbell, Jessica; Hibshoosh, Hanina; Crew, Katherine; Kalinsky, Kevin; Hershman, Dawn L.; Hielscher, Andreas H.
ISI:000401132900012
ISSN: 0277-786x
CID: 5390402

Fast linear solver for radiative transport equation with multiple right hand sides in diffuse optical tomography

Jia, Jingfei; Kim, Hyun K; Hielscher, Andreas H
It is well known that radiative transfer equation (RTE) provides more accurate tomographic results than its diffusion approximation (DA). However, RTE-based tomographic reconstruction codes have limited applicability in practice due to their high computational cost. In this article, we propose a new efficient method for solving the RTE forward problem with multiple light sources in an all-at-once manner instead of solving it for each source separately. To this end, we introduce here a novel linear solver called block biconjugate gradient stabilized method (block BiCGStab) that makes full use of the shared information between different right hand sides to accelerate solution convergence. Two parallelized block BiCGStab methods are proposed for additional acceleration under limited threads situation. We evaluate the performance of this algorithm with numerical simulation studies involving the Delta-Eddington approximation to the scattering phase function. The results show that the single threading block RTE solver proposed here reduces computation time by a factor of 1.5~3 as compared to the traditional sequential solution method and the parallel block solver by a factor of 1.5 as compared to the traditional parallel sequential method. This block linear solver is, moreover, independent of discretization schemes and preconditioners used; thus further acceleration and higher accuracy can be expected when combined with other existing discretization schemes or preconditioners.
PMCID:4556172
PMID: 26345531
ISSN: 0022-4073
CID: 5390012

Detection of Peripheral Arterial Disease Within the Foot Using Vascular Optical Tomographic Imaging: A Clinical Pilot Study

Khalil, M A; Kim, H K; Hoi, J W; Kim, I; Dayal, R; Shrikhande, G; Hielscher, A H
OBJECTIVE:Vascular optical tomographic imaging (VOTI) is a novel imaging modality that is capable of detecting hemoglobin concentrations in tissue. VOTI is non-invasive, non-ionizing and does not require contrast injection. This technology was applied to the diagnosis of peripheral arterial disease (PAD) within lower extremities of diabetic patients with calcified arteries. This could be of substantial benefit as these patients suffer from comorbidities such as arterial incompressibility, which complicates diagnosis and monitoring. METHODS:Forty individuals (10 non-diabetic patients with PAD, 10 diabetic patients with PAD, and 20 healthy volunteers) were enrolled in a diagnostic pilot study using the VOTI system. The patients were imaged during at high pressure cuff occlusion. RESULTS:The VOTI system was capable of quantifying the blood volume changes within the foot during the thigh cuff occlusion and outputting diagnostic parameters, such as change in hemoglobin concentration, enabling the assessment of foot perfusion. This study resulted in a statistically significant difference between the healthy cohort and both the non-diabetic and the diabetic PAD cohorts (p = .006, p = .006). Receiver operating characteristic (ROC) curve analysis showed that PAD diagnosis could be made with over 80% sensitivity or specificity depending on the characteristic cutoff point. In addition, VOTI was capable of providing the locations of under-perfused regions within the foot and evaluating the severity of arterial disease, even within diabetic patients with calcified arteries, who are traditionally difficult to diagnose. CONCLUSION/CONCLUSIONS:VOTI can effectively diagnose PAD independently of arterial compressibility, making it very useful for assessing vascular disease in diabetic patients.
PMCID:4439381
PMID: 25457299
ISSN: 1532-2165
CID: 5390002

Modeling of the blood flow in the lower extremities for dynamic diffuse optical tomography of Peripheral Artery Disease [Meeting Abstract]

Marone, A.; Hoi, J. W.; Khalil, M. A.; Kim, H. K.; Shrikhande, G.; Dayal, R.; Hielscher, A. H.
ISI:000359294500020
ISSN: 0277-786x
CID: 5390372

Combined Dynamic and Static Optical Tomography for Prediction of Treatment outcome in Breast Cancer Patients [Meeting Abstract]

Gunther, Jacqueline; Lim, Emerson; Kim, Hyun Keol; Flexman, Molly; Zweck, Lukas; Arora, Sindhiya; Refice, Susan; Brown, Mindy; Kalinsky, Kevin; Hershman, Dawn; Hielscher, Andreas H.
ISI:000359294500021
ISSN: 0277-786x
CID: 5390382