Lothar Lilge - Academia.edu (original) (raw)

Papers by Lothar Lilge

Proceedings of SPIE, Jul 7, 1993

Median survival for Glioblastoma patients remains at around 15 months after surgery, radiation, a... more Median survival for Glioblastoma patients remains at around 15 months after surgery, radiation, and chemotherapy but varies widely between surgeons and centres. Interstitial Photodynamic Therapy (iPDT) mediated by ALA induced PpIX or other photosensitizers is investigated at various clinics. To enable iPDT treatment planning, photosensitizer transport characteristics needs to be known in order to optimize photoactivation. A method using contrast enhanced, functional magnetic resonance imaging, compartment modelling, spatial frequency domain imaging (SFDI) and inductively coupled plasma mass spectrometry (ICP-MS) is proposed to predict and validate the localization characteristics of two photosensitizers in murine Glioblastoma models.

Proceedings of SPIE, Jun 30, 2005

ABSTRACT A primary goal of preventive oncology is the identification of women at increased risk f... more ABSTRACT A primary goal of preventive oncology is the identification of women at increased risk for breast cancer who would benefit most from risk reducing interventions. An established physical risk assessment technique is the use of mammography to quantify the dense tissue content of the breast. Women with a majority of the breast occupied by dense tissue are at four to six times greater risk of breast cancer than women with the least density. The main drawback of mammography is that it requires exposure to ionising radiation and there are concerns regarding use in young women. Another potential physical risk assessment is Transillumination Breast Spectroscopy (TIBS). TIBS uses non-ionizing optical radiation to measure bulk tissue properties and thus is applicable to women of any age. This study examines the feasibility of using TIBS in vivo to detect mammographic density as an interim indicator of breast cancer risk. TIBS measurements were completed on 300 women with radiological normal mammograms. White light (625 to 1060 nm) was delivered to the breast tissue and transmitted light was detected on the opposite side of the breast. Principal component analysis was used to reduce the spectral data and generate individual 'risk' scores. Agreement between the obtained 'risk' scores and mammographic density was established using density cluster analysis, the Kappa statistic and logistic regression. The agreement between breast density assessed by mammography and by TIBS was statistically significant for all 'risk' scores. Logistic regression indicated a strong association between the TIBS scores and mammographic density. TIBS provides an alternative to x-ray derived mammographic density as a biomarker of breast density and hence cancer risk.

Proceedings of SPIE, Sep 28, 2005

ABSTRACT

The simulation of light propagation through tissues is important for medical applications, such a... more The simulation of light propagation through tissues is important for medical applications, such as photodynamic therapy (PDT) for cancer treatment. To optimize PDT an inverse problem, which works backwards from a desired distribution of light to the parameters that caused it, must be solved. These problems have no closed-form solution and therefore must be solved numerically using an iterative method. This involves running many forward light propagation simulations which is time-consuming and computationally intensive. Currently, the fastest general software solver for this problem is FulMonteSW. It models complex 3D geometries with tetrahedral meshes and uses Monte Carlo techniques to model photon interactions with tissues. This work presents FullMonteFPGACL: an FPGA-accelerated version of FullMonteSW using an Intel Stratix 10 FPGA and the Intel FPGA SDK for OpenCL. FullMonteFPGACL has been validated and benchmarked using several models and achieves improvements in performance (4x) and energy-efficiency (11x) over the optimized and multi-threaded FullMonteSW implementation. We discuss methods for extending the design to improve the performance and energy-efficiency ratios to 16x and 17x, respectively. We achieved these gains by developing in an agile fashion using OpenCL to facilitate quick prototyping and hardware-software partitioning. However, achieving competitive area and performance required careful design of the hardware pipeline and expression of its structure in OpenCL. This led to a hybrid design style that can improve productivity when developing complex applications on an FPGA.

ABSTRACT Microvascular pattern was estimated via lens-less image acquisition from intralipid/micr... more ABSTRACT Microvascular pattern was estimated via lens-less image acquisition from intralipid/microfluidic phantom. The CMOS chip provided proficient images of subsurface structures - microchannels filled out by haemoglobin disguised under layer of Intralipid.

European urology open science, Jul 1, 2022

Journal of Biomedical Optics, Aug 10, 2018

We introduce the FullMonte tetrahedral 3-D Monte Carlo (MC) software package for simulation, visu... more We introduce the FullMonte tetrahedral 3-D Monte Carlo (MC) software package for simulation, visualization, and analysis of light propagation in heterogeneous turbid media including tissue. It provides the highest computational performance and richest set of input, output, and analysis facilities of any open-source tetrahedral-mesh MC light simulator. It also provides a robust framework for statistical verification. A scripting interface makes setup of simulation runs simple, including parameter sweeps, while simultaneously providing customization options. Data formats shared with class-leading visualization tools, VTK and Paraview, facilitate interactive generation of publication-quality fluence and irradiance maps. The simulator can read and write file formats supported by other similar simulators, such as TIM-OS, MMC, COMSOL (finite-element simulations), and MCML to support comparison. Where simulator features permit, FullMonte can take a single test case, run it in multiple software packages, and load the results together for comparison. Example meshes, optical properties, setup scripts, and output files are provided for user convenience. We demonstrate its use in several test cases, including photodynamic therapy of the brain, bioluminescence imaging (BLI) in a mouse phantom, and a comparison against MCML for layered geometries. Application domains that can benefit from use of FullMonte include photodynamic, photothermal, and photobiomodulation therapies, BLI, diffuse optical tomography, MC software development, and biophotonics education. Since MC results may be used for preclinical or even clinical experiments, a robust and rigorous verification process is essential. Being a stochastic numerical method, MC simulation has unique challenges associated with verification of output results since observed differences may be due simply to output variance or actual differences in expected output. We describe and have implemented a rigorous and statistically justified framework for comparing between simulators of the same class and for performing regression testing.

Cancer Prevention Research, Jul 1, 2020

Polycyclic aromatic hydrocarbons (PAH) are common environmental pollutants that result from incom... more Polycyclic aromatic hydrocarbons (PAH) are common environmental pollutants that result from incomplete combustion of biomass and fossil fuels. PAH have endocrine-disrupting properties and are known animal carcinogens. Evidence from case-control studies suggests an association between PAH and breast cancer risk, but longitudinal research on PAH exposure during critical windows of susceptibility, such as prenatally and in early life, is limited. The purpose of this study was to prospectively examine whether prenatal exposure to PAH is associated with breast tissue composition, an intermediate marker of breast cancer risk, in adolescent girls. We studied 105 adolescent girls in the Columbia Center for Children’s Environmental Health (CCCEH) birth cohort, which recruited nonsmoking African American and Dominican American pregnant women living in three low-income neighborhoods in New York City from 1998-2006. Women wore a small backpack holding a personal air monitor for 2 consecutive days during the 3rd trimester of pregnancy, which measured concentrations of pyrene and 8 other carcinogenic PAH (summed and categorized into tertiles for analysis). Girls completed a follow-up clinic visit in adolescence (ages 11.2-19.6 years, median=15.8), at which time breast tissue composition was measured by optical spectroscopy (OS). OS is a novel and noninvasive tool that provides a broad compositional view of the breast by capturing variation in the amount of water, lipid, oxy-hemoglobin, deoxy-hemoglobin, and collagen, as well as overall cellular and connective tissue density. OS measured red and near-infrared light transmission of 7 wavelengths (650-1060 nm) at 4 source-detector distances in each breast quadrant, resulting in 16 overlapping tissue volumes. Principal component analysis was used to reduce spectral data and generate principal component (PC) scores for each participant, which were averaged over both breasts. We used multivariable linear regression to examine associations of prenatal PAH measures (pyrene and Σ8 PAH) with each of the first 4 OS PCs, which explained >99% of the spectral variation in the sample. Models were adjusted for age, ethnicity, body mass index (BMI) at time of OS measurement, age at breast development, and mothers’ prepregnancy BMI. After adjusting for covariates, PC1 scores were significantly lower on average in the highest compared to lowest tertile of prenatal ambient Σ8 PAH (β = -0.42, 95% CI = -0.81 to -0.02, p = 0.04). PC1 covered 91.8% of the spectral variations and represents overall light attenuation from higher scattering due to higher cellularity and connective tissues. PC1 also mapped to multiple chromophores including hemoglobin and collagen. No associations were found between prenatal ambient Σ8 PAH and PCs 2-4, and no associations with OS PCs were found for pyrene. To conclude, we found evidence suggesting that prenatal exposure to PAH is associated with breast tissue composition in adolescent girls. Citation Format: Rebecca D. Kehm, Lothar Lilge, E. Jane Walter, Nur Zeinomar, Jasmine A. McDonald, Parisa Tehranifar, Julie B. Herbstman, Rachel L. Miller, Mary Beth Terry. Prenatal exposure to polycyclic aromatic hydrocarbons and breast tissue composition in adolescent girls [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A15.

Conference on Lasers and Electro-Optics, May 16, 2004

... Chen, Jürgen Ihlemann, Gerd Marowsky, Peter Oesterlin and Berthold Burghardt, High-Resolutio... more ... Chen, Jürgen Ihlemann, Gerd Marowsky, Peter Oesterlin and Berthold Burghardt, High-Resolution F2-Laser Machining of Micro-Optic Components, in Photon Processing in Microelectronics and Photonics, SPIE 4637, 228-234 (2002). 3. Nigel Munce, Enabling Technologies ...

Journal of Innovative Optical Health Sciences, Jul 1, 2022

Treatment planning is of utmost importance in interstitial photodynamic therapy, as it predicts t... more Treatment planning is of utmost importance in interstitial photodynamic therapy, as it predicts the required light delivery to the target volume in an upcoming treatment. However, planning remains a major challenge due to several uncertainties such as the tissue optical properties and the concentrations of the photosensitizer and oxygen. Any difference in these parameters from the assumed values during planning could significantly affect the outcome of the actual treatment. This work introduces PDT-SPACE, a PDT light source power allocation using a convex optimization engine to minimize damage to organs-at-risk (OAR) with robustness against variation in tissue optical properties. Three power allocation methods are proposed and compared with respect to the resulting standard deviation in the damage to organs-at-risk and their runtime. The proposed approaches are demonstrated for ALA induced PpIX as photosensitizer in a virtual brain tumor that models a glioblastoma multiforme case. Results show that choosing a power allocation to minimize the OAR damage standard deviation under optical property variation tends to also minimize the tumor coverage as there is only one degree of freedom to optimize upon. This motivates simultaneous source position and power allocation optimization.

Biomicrofluidics, Feb 28, 2012

Chemical cytometry on a single cell level is of interest to various biological fields ranging fro... more Chemical cytometry on a single cell level is of interest to various biological fields ranging from cancer to stem cell research. The impact chemical cytometry can exert in these fields depends on the dimensionality of the retrievable analytes content. To this point, the number of different analytes identifiable and additionally their subcellular localization is of interest. To address this, we present an electroporation based approach for selective lysis of only the plasma membrane, which permits analysis of the dissolved cytoplasm, while reducing contributions from the nucleus and membrane bound fractions of the cell analytes. The use of 100 ls long pulse and a well defined DC electric field gradient of $4.5 kVÁcm À1 generated by 3D electrodes initiates release of a cytoplasm marker in (1 s, while retaining nuclear fluorescence markers.

Physics in Medicine and Biology, Sep 17, 2014

Doxorubicin (Dox) is a well-established chemotherapeutic agent, however it has limited efficacy i... more Doxorubicin (Dox) is a well-established chemotherapeutic agent, however it has limited efficacy in treating brain malignancies due to the presence of the blood-brain barrier (BBB). Recent preclinical studies have demonstrated that focused ultrasound induced BBB disruption (BBBD) enables efficient delivery of Dox to the brain. For future treatment planning of BBBD-based drug delivery, it is crucial to establish a mathematical framework to predict the effect of transient BBB permeability enhancement on the spatiotemporal distribution of Dox at the targeted area. The constructed model considers Dox concentrations within three compartments (plasma, extracellular, intracellular) that are governed by various transport processes (e.g. diffusion in interstitial space, exchange across vessel wall, clearance by cerebral spinal fluid, uptake by brain cells). By examining several clinical treatment aspects (e.g. sonication scheme, permeability enhancement, injection mode), our simulation results support the experimental findings of optimal interval delay between two consecutive sonications and therapeutically-sufficient intracellular concentration with respect to transfer constant Ktrans range of 0.01-0.03 min(-1). Finally, the model suggests that infusion over a short duration (20-60 min) should be employed along with single-sonication or multiple-sonication at 10 min interval to ensure maximum delivery to the intracellular compartment while attaining minimal cardiotoxicity via suppressing peak plasma concentration.

Analytical Chemistry, Jul 28, 2004

Performing single-cell electrophoresis separations using multiple parallel microchannels offers t... more Performing single-cell electrophoresis separations using multiple parallel microchannels offers the possibility of both increasing throughput and eliminating cross-contamination between different separations. The instrumentation for such a system requires spatial and temporal control of both single-cell selection and lysis. To address these problems, a compact platform is presented for single-cell capillary electrophoresis in parallel microchannels that combines optical tweezers for cell selection and electromechanical lysis. Calcein-labeled acute myloid leukemia (AML) cells were selected from an on-chip reservoir and transported by optical tweezers to one of four parallel microfluidic channels. Each channel entrance was manufactured by F 2-laser ablation to form a 20-to 10-µm tapered lysis reservoir, creating an injector geometry effective in confining the cellular contents during mechanical shearing of the cell at the 10-µm capillary entrance. The contents of individual cells were simultaneously injected into parallel channels resulting in electrophoretic separation as recorded by laser-induced fluorescence of the labeled cellular contents.

Photochemical and Photobiological Sciences, Nov 1, 2015

The photo-physical and photo-biological properties of two small (<2 kDa), novel Ru(II) photosensi... more The photo-physical and photo-biological properties of two small (<2 kDa), novel Ru(II) photosensitizers (PSs) referred to as TLD1411 and TLD1433 are presented. Both PSs are highly water-soluble, provide only very limited luminescence emission at 580-680 nm following excitation at 530 nm, and demonstrate high photostability with less than 50% photobleaching at radiant exposures H = 275 J cm −2 (530 nm irradiation). It was previously shown that these two photosensitizers exhibit a large singlet oxygen (1 O 2) quantum yield (Φ (Δ) ∼0.99 in acetonitrile). Their photon-mediated efficacy to cause cell death (λ = 530 nm, H = 45 J cm −2) was tested in vitro in colon and glioma cancer cell lines (CT26.WT, CT26.CL25, F98, and U87) and demonstrated a strong photodynamic effect with complete cell death at concentrations as low as 4 and 1 μM for TLD1411 and TLD1433, respectively. Notably, dark toxicity was negligible at concentrations less than 25 and 10 μM for TLD1411 and TLD1433, respectively. The ability of the PSs to initiate Type I photoreactions was tested by exposing PS-treated U87 cells to light under hypoxic conditions (pO 2 < 0.5%), which resulted in a complete loss of the PDT effect. In vivo, the maximum tolerated doses 50 (MTD50) were determined to be 36 mg kg −1 (TLD1411) and 103 mg kg −1 (TLD1433) using the BALB/c murine model. In vivo growth delay studies in the subcutaneous colon adenocarcinoma CT26.WT murine model were conducted at a photosensitizer dose equal to 0.5 and 0.2 MTD50 for TLD1411 and TLD1433, respectively. 4 hours post PS injection, tumours were irradiated with continuous wave or pulsed light sources (λ = 525-530 nm, H = 192 J cm −2). Overall, treatment with continuous wave light demonstrated a higher tumour destruction efficacy when compared to pulsed light. TLD1433 mediated PDT resulted in statistically significant longer animal survival compared to TLD1411. Two-thirds of TLD1433treated mice survived more than 100 days (p < 0.01) whereas TLD1411-treated mice did not survive longer than 20 days. Here we present evidence that two novel PSs have very potent photo-biological properties and are able to cause PDT-mediated cell death in both in vitro cell culture models and in vivo tumour regression. † Electronic supplementary information (ESI) available. See

Supplementary Table S3 shows the characteristics of adult women by maternal education at birth in... more Supplementary Table S3 shows the characteristics of adult women by maternal education at birth in the Columbia Breast Cancer and the Environment Research Program (Columbia-BCERP) Study, n = 160.

Supplementary Figure S1 shows how adolescent girls in the study were classified into the composit... more Supplementary Figure S1 shows how adolescent girls in the study were classified into the composite socioeconomic status index based on their annual household income and maternal education at birth.

Cancer Epidemiology, Biomarkers & Prevention, Aug 2, 2023

Background: Socioeconomic status (SES) at birth is associated with breast cancer risk. Whether th... more Background: Socioeconomic status (SES) at birth is associated with breast cancer risk. Whether this association is driven by changes in breast tissue composition (BTC) prior to adulthood remains unclear. Methods: We used multivariable linear regression models to examine whether SES at birth is associated with BTC in adolescence and adulthood using data from a New York City cohort of daughters (n = 165, 11–20 years) and mothers (n = 160, 29–55 years). We used maternal-reported data on daughters’ household income and maternal education at birth, analyzed individually and in combination (SES index). Women also reported their own mothers’ education at birth. We used optical spectroscopy to evaluate BTC measures that positively (water content, collagen content, optical index) and negatively (lipid content) correlate with mammographic breast density, a recognized breast cancer risk factor. Results: Being in the highest versus lowest category of the SES index was associated with lower lipid content [βadjusted (βadj) = −0.80; 95% confidence interval (CI), −1.30 to –0.31] and higher collagen content (βadj = 0.54; 95% CI, 0.09–0.99) in adolescence. In women with a body mass index (BMI) <30 kg/m2, higher maternal education at birth (≥ vs. < high school degree) was associated with lower lipid content (βadj = −0.57; 95% CI, −0.97 to −0.17), higher water content (βadj = 0.70; 95% CI, 0.26–1.14), and higher optical index (βadj = 0.53; 95% CI, 0.10–0.95). Conclusions: This study supports that SES at birth is associated with BTC in adolescence and adulthood, although the latter association may depend on adult BMI. Impact: Further research is needed to identify the socially patterned early life factors influencing BTC.