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Studies of cortical function in newborn infants in clinical settings are extremely challenging to undertake with traditional neuroimaging approaches. Partly in response to this challenge, functional near-infrared spectroscopy (fNIRS) has become an increasingly common clinical research tool but has significant limitations including a low spatial resolution and poor depth specificity. Moreover, the bulky optical fibres required in traditional fNIRS approaches present significant mechanical challenges, particularly for the study of vulnerable newborn infants. A new generation of wearable, modular, high-density diffuse optical tomography (HD-DOT) technologies has recently emerged that overcomes many of the limitations of traditional, fibre-based and low-density fNIRS measurements. Driven by the development of this new technology, we have undertaken the first cot-side study of newborn infants using wearable HD-DOT in a clinical setting. We use this technology to study functional brain connectivity (FC) in newborn infants during sleep and assess the effect of neonatal sleep states, active sleep (AS) and quiet sleep (QS), on resting state FC. Our results demonstrate that it is now possible to obtain high-quality functional images of the neonatal brain in the clinical setting with few constraints. Our results also suggest that sleep states differentially affect FC in the neonatal brain, consistent with prior reports.
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Mapeo Encefálico , Tomografía Óptica , Recién Nacido , Humanos , Mapeo Encefálico/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Cabeza , Tomografía Óptica/métodos , SueñoRESUMEN
BACKGROUND: When characterizing the brain's resting state functional connectivity (RSFC) networks, demonstrating networks' similarity across sessions and reliability across different scan durations is essential for validating results and possibly minimizing the scanning time needed to obtain stable measures of RSFC. Recent advances in optical functional neuroimaging technologies have resulted in fully wearable devices that may serve as a complimentary tool to functional magnetic resonance imaging (fMRI) and allow for investigations of RSFC networks repeatedly and easily in non-traditional scanning environments. METHODS: Resting-state cortical hemodynamic activity was repeatedly measured in a single individual in the home environment during COVID-19 lockdown conditions using the first ever application of a 24-module (72 sources, 96 detectors) wearable high-density diffuse optical tomography (HD-DOT) system. Twelve-minute recordings of resting-state data were acquired over the pre-frontal and occipital regions in fourteen experimental sessions over three weeks. As an initial validation of the data, spatial independent component analysis was used to identify RSFC networks. Reliability and similarity scores were computed using metrics adapted from the fMRI literature. RESULTS: We observed RSFC networks over visual regions (visual peripheral, visual central networks) and higher-order association regions (control, salience and default mode network), consistent with previous fMRI literature. High similarity was observed across testing sessions and across chromophores (oxygenated and deoxygenated haemoglobin, HbO and HbR) for all functional networks, and for each network considered separately. Stable reliability values (described here as a <10% change between time windows) were obtained for HbO and HbR with differences in required scanning time observed on a network-by-network basis. DISCUSSION: Using RSFC data from a highly sampled individual, the present work demonstrates that wearable HD-DOT can be used to obtain RSFC measurements with high similarity across imaging sessions and reliability across recording durations in the home environment. Wearable HD-DOT may serve as a complimentary tool to fMRI for studying RSFC networks outside of the traditional scanning environment and in vulnerable populations for whom fMRI is not feasible.
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COVID-19 , Tomografía Óptica , Humanos , Mapeo Encefálico/métodos , Reproducibilidad de los Resultados , Control de Enfermedades Transmisibles , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Descanso , Red Nerviosa/diagnóstico por imagenRESUMEN
Inhibitory control, a core executive function, emerges in infancy and develops rapidly across childhood. Methodological limitations have meant that studies investigating the neural correlates underlying inhibitory control in infancy are rare. Employing functional near-infrared spectroscopy alongside a novel touchscreen task that measures response inhibition, this study aimed to uncover the neural underpinnings of inhibitory control in 10-month-old infants (N = 135). We found that when inhibition was required, the right prefrontal and parietal cortices were more activated than when there was no inhibitory demand. This demonstrates that inhibitory control in infants as young as 10 months of age is supported by similar brain areas as in older children and adults. With this study we have lowered the age-boundary for localising the neural substrates of response inhibition to the first year of life.
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Corteza Prefrontal , Espectroscopía Infrarroja Corta , Adulto , Niño , Función Ejecutiva/fisiología , Humanos , Lactante , Inhibición Psicológica , Lóbulo Parietal/fisiología , Corteza Prefrontal/fisiología , Espectroscopía Infrarroja Corta/métodosRESUMEN
The first 1000 days from conception to two-years of age are a critical period in brain development, and there is an increasing drive for developing technologies to help advance our understanding of neurodevelopmental processes during this time. Functional near-infrared spectroscopy (fNIRS) has enabled longitudinal infant brain function to be studied in a multitude of settings. Conventional fNIRS analyses tend to occur in the channel-space, where data from equivalent channels across individuals are combined, which implicitly assumes that head size and source-detector positions (i.e. array position) on the scalp are constant across individuals. The validity of such assumptions in longitudinal infant fNIRS analyses, where head growth is most rapid, has not previously been investigated. We employed an image reconstruction approach to analyse fNIRS data collected from a longitudinal cohort of infants in The Gambia aged 5- to 12-months. This enabled us to investigate the effect of variability in both head size and array position on the anatomical and statistical inferences drawn from the data at both the group- and the individual-level. We also sought to investigate the impact of group size on inferences drawn from the data. We found that variability in array position was the driving factor between differing inferences drawn from the data at both the individual- and group-level, but its effect was weakened as group size increased towards the full cohort size (N = 53 at 5-months, N = 40 at 8-months and N = 45 at 12-months). We conclude that, at the group sizes in our dataset, group-level channel-space analysis of longitudinal infant fNIRS data is robust to assumptions about head size and array position given the variability in these parameters in our dataset. These findings support a more widespread use of image reconstruction techniques in longitudinal infant fNIRS studies.
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Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/fisiología , Desarrollo Infantil/fisiología , Neuroimagen Funcional/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Espectroscopía Infrarroja Corta/métodos , Percepción Auditiva/fisiología , Corteza Cerebral/crecimiento & desarrollo , Gambia , Humanos , Lactante , Estudios Longitudinales , Percepción Social , Percepción Visual/fisiologíaRESUMEN
Studies of cortical function in the awake infant are extremely challenging to undertake with traditional neuroimaging approaches. Partly in response to this challenge, functional near-infrared spectroscopy (fNIRS) has become increasingly common in developmental neuroscience, but has significant limitations including resolution, spatial specificity and ergonomics. In adults, high-density arrays of near-infrared sources and detectors have recently been shown to yield dramatic improvements in spatial resolution and specificity when compared to typical fNIRS approaches. However, most existing fNIRS devices only permit the acquisition of ~20-100 sparsely distributed fNIRS channels, and increasing the number of optodes presents significant mechanical challenges, particularly for infant applications. A new generation of wearable, modular, high-density diffuse optical tomography (HD-DOT) technologies has recently emerged that overcomes many of the limitations of traditional, fibre-based and low-density fNIRS measurements. Driven by the development of this new technology, we have undertaken the first study of the infant brain using wearable HD-DOT. Using a well-established social stimulus paradigm, and combining this new imaging technology with advances in cap design and spatial registration, we show that it is now possible to obtain high-quality, functional images of the infant brain with minimal constraints on either the environment or on the infant participants. Our results are consistent with prior low-density fNIRS measures based on similar paradigms, but demonstrate superior spatial localization, improved depth specificity, higher SNR and a dramatic improvement in the consistency of the responses across participants. Our data retention rates also demonstrate that this new generation of wearable technology is well tolerated by the infant population.
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Encéfalo/diagnóstico por imagen , Tomografía Óptica/instrumentación , Dispositivos Electrónicos Vestibles , Encéfalo/crecimiento & desarrollo , Femenino , Neuroimagen Funcional , Humanos , Imagenología Tridimensional/instrumentación , Imagenología Tridimensional/métodos , Lactante , Masculino , Relación Señal-Ruido , Espectroscopía Infrarroja Corta , Tomografía Óptica/métodosRESUMEN
The neonatal brain undergoes dramatic structural and functional changes over the last trimester of gestation. The accuracy of source localisation of brain activity recorded from the scalp therefore relies on accurate age-specific head models. Although an age-appropriate population-level atlas could be used, detail is lost in the construction of such atlases, in particular with regard to the smoothing of the cortical surface, and so such a model is not representative of anatomy at an individual level. In this work, we describe the construction of a database of individual structural priors of the neonatal head using 215 individual-level datasets at ages 29-44 weeks postmenstrual age from the Developing Human Connectome Project. We have validated a method to segment the extra-cerebral tissue against manual segmentation. We have also conducted a leave-one-out analysis to quantify the expected spatial error incurred with regard to localising functional activation when using a best-matching individual from the database in place of a subject-specific model; the median error was calculated to be 8.3 mm (median absolute deviation 3.8 mm). The database can be applied for any functional neuroimaging modality which requires structural data whereby the physical parameters associated with that modality vary with tissue type and is freely available at www.ucl.ac.uk/dot-hub.
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Encéfalo/diagnóstico por imagen , Neuroimagen/métodos , Encéfalo/anatomía & histología , Encéfalo/fisiología , Bases de Datos Factuales , Neuroimagen Funcional/métodos , Edad Gestacional , Humanos , Recién Nacido , Neuroimagen/normasRESUMEN
Functional near-infrared spectroscopy (fNIRS) is a widely used imaging method for mapping brain activation based on cerebral hemodynamics. The accurate quantification of cortical activation using fNIRS data is highly dependent on the ability to correctly localize the positions of light sources and photodetectors on the scalp surface. Variations in head size and shape across participants greatly impact the precise locations of these optodes and consequently, the regions of the cortical surface being reached. Such variations can therefore influence the conclusions drawn in NIRS studies that attempt to explore specific cortical regions. In order to preserve the spatial identity of each NIRS channel, subject-specific differences in NIRS array registration must be considered. Using high-density diffuse optical tomography (HD-DOT), we have demonstrated the inter-subject variability of the same HD-DOT array applied to ten participants recorded in the resting state. We have also compared three-dimensional image reconstruction results obtained using subject-specific positioning information to those obtained using generic optode locations. To mitigate the error introduced by using generic information for all participants, photogrammetry was used to identify specific optode locations per-participant. The present work demonstrates the large variation between subjects in terms of which cortical parcels are sampled by equivalent channels in the HD-DOT array. In particular, motor cortex recordings suffered from the largest optode localization errors, with a median localization error of 27.4 mm between generic and subject-specific optodes, leading to large differences in parcel sensitivity. These results illustrate the importance of collecting subject-specific optode locations for all wearable NIRS experiments, in order to perform accurate group-level analysis using cortical parcellation.
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We demonstrate four wave mixing (FWM) based wavelength conversion of 40 Gbaud differential phase shift keyed (DPSK) and quadrature phase shift keyed (QPSK) signals in a 2.5 cm long silicon germanium waveguide. For a 290 mW pump power, bit error ratio (BER) measurements show approximately a 2-dB power penalty in both cases of DPSK (measured at a BER of 10(-9)) and QPSK (at a BER of 10(-3)) signals that we examined.
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Germanio/química , Procesamiento de Señales Asistido por Computador/instrumentación , Silicio/química , Resonancia por Plasmón de Superficie/instrumentación , Telecomunicaciones/instrumentación , Diseño de Equipo , Análisis de Falla de Equipo , MicroondasRESUMEN
Significance: Dementia presents a global healthcare crisis, and neuroimaging is the main method for developing effective diagnoses and treatments. Yet currently, there is a lack of sensitive, portable, and low-cost neuroimaging tools. As dementia is associated with vascular and metabolic dysfunction, near-infrared spectroscopy (NIRS) has the potential to fill this gap. Aim: This future perspective aims to briefly review the use of NIRS in dementia to date and identify the challenges involved in realizing the full impact of NIRS for dementia research, including device development, study design, and data analysis approaches. Approach: We briefly appraised the current literature to assess the challenges, giving a critical analysis of the methods used. To assess the sensitivity of different NIRS device configurations to the brain with atrophy (as is common in most forms of dementia), we performed an optical modeling analysis to compare their cortical sensitivity. Results: The first NIRS dementia study was published in 1996, and the number of studies has increased over time. In general, these studies identified diminished hemodynamic responses in the frontal lobe and altered functional connectivity in dementia. Our analysis showed that traditional (low-density) NIRS arrays are sensitive to the brain with atrophy (although we see a mean decrease of 22% in the relative brain sensitivity with respect to the healthy brain), but there is a significant improvement (a factor of 50 sensitivity increase) with high-density arrays. Conclusions: NIRS has a bright future in dementia research. Advances in technology - high-density devices and intelligent data analysis-will allow new, naturalistic task designs that may have more clinical relevance and increased reproducibility for longitudinal studies. The portable and low-cost nature of NIRS provides the potential for use in clinical and screening tests.
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Over the past several decades, near-infrared spectroscopy (NIRS) has become a popular research and clinical tool for non-invasively measuring the oxygenation of biological tissues, with particular emphasis on applications to the human brain. In most cases, NIRS studies are performed using continuous-wave NIRS (CW-NIRS), which can only provide information on relative changes in chromophore concentrations, such as oxygenated and deoxygenated hemoglobin, as well as estimates of tissue oxygen saturation. Another type of NIRS known as frequency-domain NIRS (FD-NIRS) has significant advantages: it can directly measure optical pathlength and thus quantify the scattering and absorption coefficients of sampled tissues and provide direct measurements of absolute chromophore concentrations. This review describes the current status of FD-NIRS technologies, their performance, their advantages, and their limitations as compared to other NIRS methods. Significant landmarks of technological progress include the development of both benchtop and portable/wearable FD-NIRS technologies, sensitive front-end photonic components, and high-frequency phase measurements. Clinical applications of FD-NIRS technologies are discussed to provide context on current applications and needed areas of improvement. The review concludes by providing a roadmap toward the next generation of fully wearable, low-cost FD-NIRS systems.
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We propose and experimentally study the passive coherent optical addition of complex modulation format signals through the use of a delay line interferometer followed by a temporal gate to increase the encoded bits per symbol and consequently, the spectral efficiency of an incident signal. Modulation format conversion and packet compression are demonstrated as two possible application examples. A variety of modulation formats can be accommodated, whereas higher compression factors can be achieved through the use of a cascade of delay line interferometers.
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We experimentally demonstrate phase regeneration of a 40-Gb/s differential phase shift keying (DPSK) signal in a 1.7-m long highly nonlinear lead silicate W-type fiber using a degenerate two-pump phase-sensitive amplifier (PSA). Results show an improvement in the Error Vector Magnitude (EVM) and a reduction of almost a factor of 2 in the phase noise of the signal after regeneration for various noise levels at the input.
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Amplificadores Electrónicos , Tecnología de Fibra Óptica/instrumentación , Procesamiento de Señales Asistido por Computador/instrumentación , Telecomunicaciones/instrumentación , Diseño de EquipoRESUMEN
We experimentally demonstrate phase-sensitive amplification in a highly nonlinear and low-dispersion lead-silicate W-type fiber. A phase-sensitive gain variation of 6 dB was observed in a 1.56-m sample of the fiber for a total input pump power of 27.7 dBm.
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Tecnología de Fibra Óptica/instrumentación , Tecnología de Fibra Óptica/métodos , Plomo/química , Fibras Ópticas , Silicatos/química , Diseño de Equipo , Fluorescencia , Telecomunicaciones/instrumentaciónRESUMEN
Significance: Early monolingual versus bilingual experience induces adaptations in the development of linguistic and cognitive processes, and it modulates functional activation patterns during the first months of life. Resting-state functional connectivity (RSFC) is a convenient approach to study the functional organization of the infant brain. RSFC can be measured in infants during natural sleep, and it allows to simultaneously investigate various functional systems. Adaptations have been observed in RSFC due to a lifelong bilingual experience. Investigating whether bilingualism-induced adaptations in RSFC begin to emerge early in development has important implications for our understanding of how the infant brain's organization can be shaped by early environmental factors. Aims: We attempt to describe RSFC using functional near-infrared spectroscopy (fNIRS) and to examine whether it adapts to early monolingual versus bilingual environments. We also present an fNIRS data preprocessing and analysis pipeline that can be used to reliably characterize RSFC in development and to reduce false positives and flawed results interpretations. Methods: We measured spontaneous hemodynamic brain activity in a large cohort ( N = 99 ) of 4-month-old monolingual and bilingual infants using fNIRS. We implemented group-level approaches based on independent component analysis to examine RSFC, while providing proper control for physiological confounds and multiple comparisons. Results: At the group level, we describe the functional organization of the 4-month-old infant brain in large-scale cortical networks. Unbiased group-level comparisons revealed no differences in RSFC between monolingual and bilingual infants at this age. Conclusions: High-quality fNIRS data provide a means to reliably describe RSFC patterns in the infant brain. The proposed group-level RSFC analyses allow to assess differences in RSFC across experimental conditions. An effect of early bilingual experience in RSFC was not observed, suggesting that adaptations might only emerge during explicit linguistic tasks, or at a later point in development.
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Significance: Neonates are a highly vulnerable population. The risk of brain injury is greater during the first days and weeks after birth than at any other time of life. Functional neuroimaging that can be performed longitudinally and at the cot-side has the potential to improve our understanding of the evolution of multiple forms of neurological injury over the perinatal period. However, existing technologies make it very difficult to perform repeated and/or long-duration functional neuroimaging experiments at the cot-side. Aim: We aimed to create a modular, high-density diffuse optical tomography (HD-DOT) technology specifically for neonatal applications that is ultra-lightweight, low profile and provides high mechanical flexibility. We then sought to validate this technology using an anatomically accurate dynamic phantom. Approach: An advanced 10-layer rigid-flexible printed circuit board technology was adopted as the basis for the DOT modules, which allows for a compact module design that also provides the flexibility needed to conform to the curved infant scalp. Two module layouts were implemented: dual-hexagon and triple-hexagon. Using in-built board-to-board connectors, the system can be configured to provide a vast range of possible layouts. Using epoxy resin, thermochromic dyes, and MRI-derived 3D-printed moulds, we constructed an electrically switchable, anatomically accurate dynamic phantom. This phantom was used to quantify the imaging performance of our flexible, modular HD-DOT system. Results: Using one particular module configuration designed to cover the infant sensorimotor system, the device provided 36 source and 48 detector positions, and over 700 viable DOT channels per wavelength, ranging from 10 to â¼ 45 mm over an area of approximately 60 cm 2 . The total weight of this system is only 70 g. The signal changes from the dynamic phantom, while slow, closely simulated real hemodynamic response functions. Using difference images obtained from the phantom, the measured 3D localization error provided by the system at the depth of the cortex was in the of range 3 to 6 mm, and the lateral image resolution at the depth of the neonatal cortex is estimated to be as good as 10 to 12 mm. Conclusions: The HD-DOT system described is ultra-low weight, low profile, can conform to the infant scalp, and provides excellent imaging performance. It is expected that this device will make functional neuroimaging of the neonatal brain at the cot-side significantly more practical and effective.
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Metabolic pathways underlying brain function remain largely unexplored during neurodevelopment, predominantly due to the lack of feasible techniques for use with awake infants. Broadband near-infrared spectroscopy (bNIRS) provides the opportunity to explore the relationship between cerebral energy metabolism and blood oxygenation/haemodynamics through the measurement of changes in the oxidation state of mitochondrial respiratory chain enzyme cytochrome-c-oxidase (ΔoxCCO) alongside haemodynamic changes. We used a bNIRS system to measure ΔoxCCO and haemodynamics during functional activation in a group of 42 typically developing infants aged between 4 and 7 months. bNIRS measurements were made over the right hemisphere over temporal, parietal and central cortical regions, in response to social and non-social visual and auditory stimuli. Both ΔoxCCO and Δ[HbO2] displayed larger activation for the social condition in comparison to the non-social condition. Integration of haemodynamic and metabolic signals revealed networks of stimulus-selective cortical regions that were not apparent from analysis of the individual bNIRS signals. These results provide the first spatially resolved measures of cerebral metabolic activity alongside haemodynamics during functional activation in infants. Measuring synchronised changes in metabolism and haemodynamics have the potential for uncovering the development of cortical specialisation in early infancy.
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OBJECTIVE: Childhood sleep-related rhythmic movement disorder (RMD) (ie, sleep-related repetitive movements involving large muscle groups) can impair sleep quality, cause local injury, and disturb household members. Previous parental reports indicate prevalence rates in children under three years of age between 5.5 and 67%. We studied the prevalence of RMD with objective home videosomnography. METHODS: Parents of 707 children having their one-year routine health check (357 male), 740 children having their two-year health check (395 male), and 17 children of unknown age (nine male), were asked if their child showed sleep-related rhythmic movements. If telephone interview confirmed likely RMD, parents completed a standardised clinical questionnaire and three nights of home videosomnography. RESULTS: At the one-year health check, 31/707 possible cases of RMD were identified [maximal prevalence: 4.38%; 95% CI (2.81, 5.89)] compared to 11/740 at the two-year check [maximal prevalence: 1.49%, 95% CI (0.61, 2.36)]. Of 42 possible cases, nine had resolved; 14 were uncontactable, or did not wish to participate, and four did not complete the study protocol. In four of 10 remaining one-year olds and four of five remaining two-year olds parental report was objectively confirmed by videosomnography. Minimal prevalence based on objective observation was therefore 0.28% [95% CI (0.08, 1.30)] at one-year check and 0.41% [95% CI (0.08, 1.24)] at two-year check. CONCLUSIONS: Prevalence of RMD in a large population of infants and toddlers was lower than previously reported (maximum prevalence 2.87%, minimum prevalence 0.34%). It is important to confirm parental report using objective measures.
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Polisomnografía , Trastornos de la Transición Sueño-Vigilia/epidemiología , Grabación de Cinta de Video , Preescolar , Familia/psicología , Femenino , Humanos , Lactante , Masculino , Prevalencia , Trastornos de la Transición Sueño-Vigilia/diagnóstico , Encuestas y CuestionariosRESUMEN
The old novae V533 Her (Nova Her 1963), DI Lac (Nova Lac 1910), and RR Pic (Nova Pic 1891) are in (or near) their quiescent stage, following their nova explosions, and continue to accrete at a high rate in the aftermath of their explosions. They exhibit continua that are steeply rising into the FUV, as well as absorption lines and emission lines of uncertain origin. All three have Far Ultraviolet Spectroscopic Explorer (FUSE) spectra that offer not only higher spectral resolution but also wavelength coverage extending down to the Lyman Limit. For DI Lac, we have matched these FUSE spectra with existing archival International Ultraviolet Explorer spectral coverage to broaden the FUV wavelength coverage. We adopted the newly determined interstellar reddening corrections of Selvelli & Gilmozzi. The dereddened FUV spectra have been modeled with our grids of optically thick accretion disks and hot, NLTE white dwarf (WD) photospheres. The results of our modeling analysis indicate that the hot components in RR Pic and V533 Her are likely to be accretion disks with mass accretion rates of 10-8Mâ yr-1 and 10-9Mâ yr-1 respectively. However, the disk cannot produce the observed absorption lines. For the WD to be the source of the absorption lines in these two systems, it must be very hot, with a radius several times its expected size (because the WD in these systems is massive, it has a smaller radius). For DI Lac, we find the best fit to be a disk with M = 10-10Mâ yr-1 with a 30,000 K WD.