Dual-wavelength Imaging Research Articles

Dual-wavelength resolution matching digital holographic microscopy using one path structured illumination

A dual-wavelength resolution-matching digital holographic microscopy with one path structured illumination is presented, which can improve phase imaging resolution. In this configuration, a dual-wavelength hologram with two illumination modes corresponding to two different wavelengths can be flexibly recorded at one shot, and the imaging resolutions under the two wavelengths can reach equivalence by setting the modulation frequency of structure illumination. The expression for calculating the modulation frequency of structured illumination in a two-wavelength system is given. By setting the proper modulation frequency, the resolution of dual-wavelength phase imaging can be enhanced, which is verified in the phase imaging experiment of a USAF quantitative phase target. The dual-wavelength reconstructed phase map of paramecia cells exhibit the internal macronucleus, food vacuole and cilia. The imaging results demonstrate the resolution-matching approach using one path structured-illumination in effect for the improvement of phase imaging resolution.

Ultra-miniature dual-wavelength spatial frequency domain imaging for micro-endoscopy.

There is a need for a cost-effective, quantitative imaging tool that can be deployed endoscopically to better detect early stage gastrointestinal cancers. Spatial frequency domain imaging (SFDI) is a low-cost imaging technique that produces near-real time, quantitative maps of absorption and reduced scattering coefficients, but most implementations are bulky and suitable only for use outside the body. We aim to develop an ultra-miniature SFDI system comprising an optical fiber array (diameter 0.125mm) and a micro camera ( package) to displace conventionally bulky components, in particular, the projector. First, we fabricated a prototype with an outer diameter of 3mm, although the individual component dimensions could permit future packaging to a diameter. We developed a phase-tracking algorithm to rapidly extract images with fringe projections at three equispaced phase shifts to perform SFDI demodulation. To validate the performance, we first demonstrate comparable recovery of quantitative optical properties between our ultra-miniature system and a conventional bench-top SFDI system with an agreement of 15% and 6% for absorption and reduced scattering, respectively. Next, we demonstrate imaging of absorption and reduced scattering of tissue-mimicking phantoms providing enhanced contrast between simulated tissue types (healthy and tumour), done simultaneously at wavelengths of 515 and 660nm. Using a support vector machine classifier, we estimate that sensitivity and specificity values of are feasible for detecting simulated squamous cell carcinoma. This device shows promise as a cost-effective, quantitative imaging tool to detect variations in optical absorption and scattering as indicators of cancer.

Vein visualization enhancement by dual-wavelength phase-locked denoising technology

Visual near-infrared imaging equipment has broad applications in various fields such as venipuncture, facial injections, and safety verification due to its noncontact, compact, and portable design. Currently, most studies utilize near-infrared single-wavelength for image acquisition of veins. However, many substances in the skin, including water, protein, and melanin can create significant background noise, which hinders accurate detection. In this paper, we developed a dual-wavelength imaging system with phase-locked denoising technology to acquire vein image. The signals in the effective region are compared by using the absorption valley and peak of hemoglobin at 700[Formula: see text]nm and 940[Formula: see text]nm, respectively. The phase-locked denoising algorithm is applied to decrease the noise and interference of complex surroundings from the images. The imaging results of the vein are successfully extracted in complex noise environment. It is demonstrated that the denoising effect on hand veins imaging can be improved with 57.3% by using our dual-wavelength phase-locked denoising technology. Consequently, this work proposes a novel approach for venous imaging with dual-wavelengths and phase-locked denoising algorithm to extract venous imaging results in complex noisy environment better.

Correlation between oxygenation status of extra-synovial tissue of wrist and disease activity in rheumatoid arthritis: a photoacoustic imaging study.

Rheumatoid arthritis (RA) is characterized by hypoxia in the synovial tissue. While photoacoustic imaging (PA) offers a method to evaluate tissue oxygenation in RA patients, studies exploring the link between extra-synovial tissue of wrist oxygenation and disease activity remain scarce. We aimed to assess synovial oxygenation in RA patients using a multimodal photoacoustic-ultrasound (PA/US) imaging system and establish its correlation with disease activity. A retrospective study was conducted on 111 patients with RA and 72 healthy controls from 2022 to 2023. Dual-wavelength PA imaging quantified oxygen saturation (So2) levels in the synovial membrane and peri-wrist region. Oxygenation states were categorised as hyperoxia, intermediate oxygenation, and hypoxia based on So2 values. The association between oxygenation levels and the clinical disease activity index was evaluated using a one-way analysis of variance, complemented by the Kruskal-Wallis test with Bonferroni adjustment. Of the patients with RA, 39 exhibited hyperoxia, 24 had intermediate oxygenation, and 48 had hypoxia in the wrist extra-synovial tissue. All of the control participants exhibited the hyperoxia status. Oxygenation levels in patients with RA correlated with clinical metrics. Patients with intermediate oxygenation had a lower disease activity index compared with those with hypoxia and hyperoxia. A significant correlation exists between wrist extra-synovial tissue oxygenation and disease activity in patients with RA.

Machine-learning-based mapping of blood oxygen saturation from dual-wavelength optoacoustic measurements

We developed a novel machine-learning-based algorithm based on a gradient boosting regressor for three-dimensional pixel-by-pixel mapping of blood oxygen saturation based on dual-wavelength optoacoustic data. Algorithm training was performed on in silico data produced from Monte-Carlo-generated absorbed light energy distributions in tissue-like vascularized media for probing wavelengths of 532 and 1064 nm and the empirical instrumental function of the optoacoustic imaging setup with further validation of the independent in silico data. In vivo optoacoustic data for rabbit-ear vasculature was employed as a testing dataset. The developed algorithm allowed in vivo blood oxygen saturation mapping and showed clear differences in blood oxygen saturation values in veins at 15 °C and 43 °C due to functional arteriovenous anastomoses. These results indicated that dual-wavelength optoacoustic imaging could serve as a cost-effective alternative to complicated multiwavelength quantitative optoacoustic imaging.

Macular pigment evaluation using dual-wavelength fundus auto-fluorescence imaging.

Macular pigment plays an important role in the reduction of oxidative stress and in preventing retinal diseases. Quick and easy measurements of the macular pigment are essential in both clinical and research settings. Dual wavelength fundus auto-fluorescence seems to be the optimal method. This study aims to investigate changes in fundus autofluorescence in patients taking daily lutein oral supplements and develop image processing methods for follow-up evaluations of the images. New devices allow us to examine fundus autofluorescence using both blue and green excitation wavelengths. This allows detection of the amount of macular pigment by subtracting these two images because the yellow pigment particles absorb blue wavelengths. We determined daily dose of 25 mg of lutein and 3 mg of zeaxanthin. Patients were followed up for 15 months at 3-month intervals. During our 15-month study, we observed a positive trend in pixel lightness values, suggesting an increase in macular pigments in the foveal area. In all patients taking daily lutein supplements, the foveal index significantly increased after six months, with a median change of 0.081. We did not observe a significant change after the first three months (0.006) and only a small change between the 6th and 12th-month visits (0.012). With appropriate patients and procedures for capturing autofluorescence images, this is a valuable technique for macular pigment evaluation in follow-up examinations using software image post-processing and analysis with commonly available hardware. To put this into everyday practice, developing tools to automate the assessment is necessary.

Multifunctional Ablative Gastrointestinal Imaging Capsule (MAGIC) for Esophagus Surveillance and Interventions.

Objective and Impact Statement: A clinically viable technology for comprehensive esophagus surveillance and potential treatment is lacking. Here, we report a novel multifunctional ablative gastrointestinal imaging capsule (MAGIC) technology platform to address this clinical need. The MAGIC technology could also facilitate the clinical translation and adoption of the tethered capsule endomicroscopy (TCE) technology. Introduction: Recently developed optical coherence tomography (OCT) TCE technologies have shown a promising potential for surveillance of Barrett's esophagus and esophageal cancer in awake patients without the need for sedation. However, it remains challenging with the current TCE technology for detecting early lesions and clinical adoption due to its suboptimal resolution, imaging contrast, and lack of visual guidance during imaging. Methods: Our technology reported here integrates dual-wavelength OCT imaging (operating at 800 and 1300 nm), an ultracompact endoscope camera, and an ablation laser, aiming to enable comprehensive surveillance, guidance, and potential ablative treatment of the esophagus. Results: The MAGIC has been successfully developed with its multimodality imaging and ablation capabilities demonstrated by imaging swine esophagus ex vivo and in vivo. The 800-nm OCT imaging offers exceptional resolution and contrast for the superficial layers, well suited for detecting subtle changes associated with early neoplasia. The 1300-nm OCT imaging provides deeper penetration, essential for assessing lesion invasion. The built-in miniature camera affords a conventional endoscopic view for assisting capsule deployment and laser ablation. Conclusion: By offering complementary and clinically viable functions in a single device, the reported technology represents an effective solution for endoscopic screening, diagnosis, and potential ablation treatment of the esophagus of a patient in an office setting.

Assessment of Oxygen Saturation in Breast Lesions Using Photoacoustic Imaging: Correlation With Benign and Malignant Disease

BackgroundHypoxia is a hallmark of breast cancer (BC). Photoacoustic (PA) imaging, based on the use of laser-generated ultrasound (US), can detect oxygen saturation (So2) in the tissues of breast lesion patients. PurposeTo measure the oxygenation status of tissue in and on both sides of the lesion in breast lesion participants using a multimodal Photoacoustic/ultrasound (PA/US) imaging system and to determine the correlation between So2 measured by PA imaging and benign or malignant disease. Materials and MethodsMultimodal PA/US imaging and gray-scale US (GSUS) of breast lesion was performed in consecutive breast lesion participants imaged in the US Outpatient Clinic between 2022 and 2023. Dual-wavelength PA imaging was used to measure the So2 value inside the lesion and on both sides of the tissue, and to distinguish benign from malignant lesions based on the So2 value. The ability of So2 to distinguish benign from malignant breast lesions was evaluated by the receiver operating characteristic curve (ROC) and the De-Long test. ResultsA total of 120 breast lesion participants (median age, 42.5 years) were included in the study. The malignant lesions exhibited lower So2 levels compared to benign lesions (malignant: 71.30%; benign: 83.81%; P < .01). Moreover, PA/US imaging demonstrates superior diagnostic results compared to GSUS, with an area under the curve (AUC) of 0.89 versus 0.70, sensitivity of 89.58% versus 85.42%, and specificity of 86.11% versus 55.56% at the So2 cut-off value of 78.85 (P < .001). The false positive rate in GSUS reduced by 30.75%, and the false negative rate diminished by 4.16% with PA /US diagnosis. Finally, the So2 on both sides tissues of malignant lesions are lower than that of benign lesions (P < .01). ConclusionPA imaging allows for the assessment of So2 within the lesions of breast lesion patients, thereby facilitating a superior distinction between benign and malignant lesions.

Correcting non-rigid intra-frame motion of laser speckle contrast imaging by heterogeneous regression analysis

Laser speckle contrast imaging (LSCI) is highly sensitive to motion artifacts. The blood flow perfusion obtained by LSCI during tissue motion is a mixture with the artifacts due to inter-frame image misalignment and intra-frame image blurring. Previous studies mainly focused on registering the inter-frame image misalignment. To correct the overestimation of blood flow produced from the non-rigid tissue motion during the exposure of one frame, we proposed a method combining the strategy of heterogeneous regression analysis with the simultaneous assessment of tissue structure and laser speckle dynamics using dual-wavelength imaging to extract the blood flow from the measured mixture LSCI signal. Both the phantom and animal experiments suggest that this correction method can significantly reduce the impact of non-rigid motion and improve the accuracy of blood flow speed measurement in LSCI.

A Novel Hybrid Retinal Blood Vessel Segmentation Algorithm for Enlarging the Measuring Range of Dual-Wavelength Retinal Oximetry

The non-invasive measurement of hemoglobin oxygen saturation (SO2) in retinal vessels is based on spectrophotometry and the absorption spectral characteristics of the tissue. The dual-wavelength retinal images are simultaneously captured via retinal oximetry. SO2 is calculated by processing a series of images and by calculating the optic density ratio of two images. However, existing SO2 research is focused on the thick vessels in the high-clarity region of retinal images. However, the thin vessels in the low-clarity region could provide significant information for the detection and diagnosis of neovascular diseases. To this end, we proposed a novel hybrid vessel segmentation algorithm. Firstly, a median filter was employed for image denoising. Secondly, high- and low-clarity region segmentation was carried out based on a clarity histogram. The vessels in the high-clarity areas were segmented after implementing a Gaussian filter, a matched filter, and morphological segmentation. Additionally, the vessels in the low-clarity areas were segmented using a guided filter, matched filtering, and dynamic threshold segmentation. Finally, the results were obtained through image merger and morphological operations. The experimental results and analysis show that the proposed method can effectively segment thick and thin vessels and can extend the measuring range of dual-wavelength retinal oximetry.

The early stage of adult ocular dominance plasticity revealed by near-infrared optical imaging of intrinsic signals

Long term monocular deprivation is considered to be necessary for the induction of significant ocular dominance plasticity in the adult visual cortex. In this study, we subjected adult mice to monocular deprivation for various durations and screened for changes in ocular dominance using dual-wavelength intrinsic signal optical imaging. We found that short-term deprivation was sufficient to cause a shift in ocular dominance and that these early-stage changes were detected only by near-infrared illumination. In addition, single-unit recordings showed that these early-stage changes primarily occurred in deep cortical layers. This early-stage ocular dominance shift was abolished by the blockade of NMDA receptors. In summary, our findings reveal an early phase of adult ocular dominance plasticity and provide the dynamics of adult plasticity.

Non-contact oxygen saturation monitoring for wound healing process using dual-wavelength simultaneous acquisition imaging system.

Here we report the fabrication of a noncontact pulse oximeter system based on a dual-wavelength imaging system and its oxygen saturation monitoring performance during wound healing. The dual-wavelength imaging system consists of 660nm and 940nm light-emitting diodes and a multi-spectral camera that simultaneously accepts visible and near-infrared images. Using the proposed system, images were acquired at 30 fps at both wavelengths, and photoplethysmography signals were extracted by specifying a specific region in the images. We removed the signals caused by small movements and smoothed them using the discrete wavelet transform and moving average filter. To confirm the feasibility of the proposed noncontact oxygen saturation system, a wound model was created using a hairless mouse and oxygen saturation was measured during wound healing. The measured values were compared and analyzed using a reflective animal pulse oximeter. Through a comparative analysis of these two devices, the error of the proposed system was evaluated and the possibility of its clinical application and wound healing monitoring through oxygen saturation measurement confirmed.

Polarization phase unwrapping by a dual-wavelength Mueller matrix imaging system.

In this Letter, we report a dual-wavelength Mueller matrix imaging system for polarization phase unwrapping, allowing simultaneous acquisition of the polarization images at 633 nm and 870 nm. After phase unwrapping, the relative error of linear retardance is controlled to be 3% and the absolute error of birefringence orientation is about 6°. We first show that polarization phase wrapping occurs when the samples are thick or present obvious birefringence effects, and further analyze the effect of phase wrapping on anisotropy parameters via Monte Carlo simulations. Then, experiments on porous alumina with different thicknesses and multilayer tapes are performed to verify the feasibility of phase unwrapping by a dual-wavelength Mueller matrix system. Finally, by comparing the temporal characteristics of linear retardance during tissue dehydration before and after phase unwrapping, we emphasize the significance of the dual-wavelength Mueller matrix imaging system not only for anisotropy analysis in static samples, but also for determining the trend in polarization properties of dynamic samples.

Photoacoustic Microscopic Imaging of Cerebral Vessels for Intensive Monitoring of Metabolic Acidosis.

Metabolic acidosis as one of the most common perioperative complications has been associated with increased risks for poor prognosis. Routine monitoring methods include blood gas analysis and electrocardiogram, which are limited by time delay effects. And the existing intravital imaging modalities are difficult to achieve in one step. Here, we present a dual-wavelength photoacoustic imaging approach to overcome this dilemma. The aim of this study was to develop a rapid approach for intensive monitoring of acid-base imbalance and cerebral oxygen metabolism. We characterized the cerebrovascular structure by label-free dual-wavelength (532 and 559nm) photoacoustic microscopy in healthy and diabetic mouse models with metabolic acidosis. Concurrently, we developed a single-vessel analysis method to accurately delineate the differential responses of small vessels and quantify the cerebral oxygenation following experimental alteration of pH. We demonstrated that there was an increasing trend in changes of vascular measurements (density, diameter, and relative hemoglobin concentration) and cerebral microvascular oxygen metabolism with the aggravation of acidosis. Furthermore, we established a clinical nomogram for the diagnosis of disease severity and yielded good discrimination ability with area under the curve of 0.920-0.967 and accuracy of 81.9-93.0%. The nomogram was also validated well in the diabetic mouse model with metabolic acidosis. Our photoacoustic imaging approach has great potential for rapid detection of metabolic acidosis and brain oxygen metabolism, which could potentially be applied as a bedside monitoring method for brain protection and timely treatment of acid-base abnormalities.

Dual-wavelength real-time simultaneous phase imaging based on off-axis interferometry

Dual-wavelength interferometry is widely used in optical measurement, including the of great significance phase imaging of transparent samples. Here, we present a dual wavelength real-time phase imaging system based on off-axis interferometry with two cameras for recording complex fields transmitted through transparent samples in a wide-field and non-intrusive manner. The method of phase unwrapping based on combing dual wavelength with Fourier transform was derived in detail. The advantage of the proposed system is, compared with single-shot dual wavelength holograms methods, that it can easily extract the complex fields at both wavelengths without consideration of spectrum overlap or needing extra optic device to create lateral shearing. For phase noise, we calculated and removed the phase signal without sample in Fourier domain, which can also ensure the measured phase accurately. Experimental results on standard sample (polystyrene microspheres) demonstrated the efficiency of this imaging system. Implementation in quantitative imaging of living cells showed the time of single-shot acquisition of samples was only 0.025s, which indicated that the system can be applied to real-time and label-free identification of phase objects.

Measuring Phagosomal pH by Fluorescence Microscopy.

Dual-wavelength and dual-fluorophore ratiometric imaging has become a powerful tool for the study of pH in intracellular compartments. It allows for the dynamic imaging of live cells while accounting for changes in the focal plane, differential loading of the fluorescent probe, and photobleaching caused by repeated image acquisitions. Ratiometric microscopic imaging has the added advantage over whole-population methods of being able to resolve individual cells and even individual organelles. In this chapter, we provide a detailed discussion of the basic principles of ratiometric imaging and its application to the measurement of phagosomal pH, including probe selection, the necessary instrumentation, and calibration methods.

Biodegradable germanium nanoparticles as contrast agents for near-infrared-II photoacoustic imaging.

Photoacoustic (PA) imaging using contrast agents with strong near-infrared-II (NIR-II, 1000-1700 nm) absorption enables deep penetration into biological tissue. Besides, biocompatibility and biodegradability are essential for clinical translation. Herein, we developed biocompatible and biodegradable germanium nanoparticles (GeNPs) with high photothermal stability as well as strong and broad absorption for NIR-II PA imaging. We first demonstrate the excellent biocompatibility of the GeNPs through experiments, including the zebrafish embryo survival rates, nude mouse body weight curves, and histological images of the major organs. Then, comprehensive PA imaging demonstrations are presented to showcase the versatile imaging capabilities and excellent biodegradability, including in vitro PA imaging which can bypass blood absorption, in vivo dual-wavelength PA imaging which can clearly distinguish the injected GeNPs from the background blood vessels, in vivo and ex vivo PA imaging with deep penetration, in vivo time-lapse PA imaging of a mouse ear for observing biodegradation, ex vivo time-lapse PA imaging of the major organs of a mouse model for observing the biodistribution after intravenous injection, and notably in vivo dual-modality fluorescence and PA imaging of osteosarcoma tumors. The in vivo biodegradation of GeNPs is observed not only in the normal tissue but also in the tumor, making the GeNPs a promising candidate for clinical NIR-II PA imaging applications.

Retinal oxygen kinetics imaging and analysis (ROKIA) based on the integration and fusion of structural-functional imaging.

The retina is one of the most metabolically active tissues in the body. The dysfunction of oxygen kinetics in the retina is closely related to the disease and has important clinical value. Dynamic imaging and comprehensive analyses of oxygen kinetics in the retina depend on the fusion of structural and functional imaging and high spatiotemporal resolution. But it's currently not clinically available, particularly via a single imaging device. Therefore, this work aims to develop a retinal oxygen kinetics imaging and analysis (ROKIA) technology by integrating dual-wavelength imaging with laser speckle contrast imaging modalities, which achieves structural and functional analysis with high spatial resolution and dynamic measurement, taking both external and lumen vessel diameters into account. The ROKIA systematically evaluated eight vascular metrics, four blood flow metrics, and fifteen oxygenation metrics. The single device scheme overcomes the incompatibility of optical design, harmonizes the field of view and resolution of different modalities, and reduces the difficulty of registration and image processing algorithms. More importantly, many of the metrics (such as oxygen delivery, oxygen metabolism, vessel wall thickness, etc.) derived from the fusion of structural and functional information, are unique to ROKIA. The oxygen kinetic analysis technology proposed in this paper, to our knowledge, is the first demonstration of the vascular metrics, blood flow metrics, and oxygenation metrics via a single system, which will potentially become a powerful tool for disease diagnosis and clinical research.

Oxygen saturation in retinal vessels and their correlation with endothelial microparticles in diabetes mellitus and/or cardiovascular disease.

Retinal oxygen supply is a critical requirement in ocular function, and when inadequate can lead to retinopathy. Endothelial dysfunction is a leading pathophysiology in diabetes and cardiovascular disease and may be assessed by endothelial microparticles (EMPs). We hypothesised links between retinal vessel oxygenation and EMPs, expecting these indices to be more adverse in those with both DM and CVD. Plasma from 34 patients with diabetes mellitus alone (DM), 40 with cardiovascular disease (CVD) alone and 36 with DM plus CVD was probed for EMPs by flow cytometry, but also for vascular markers soluble E-selectin (sEsel) and von Willebrand factor (vWf) (both ELISA). Retinal vessel fractal dimension, lacunarity, calibres and oxygen saturation were assessed from monochromatic and dual wavelength imaging respectively, intra-ocular pressure by was measured by rebound tonometry (I-CARE). There was no difference in oxygenation (arterial p=0.725, venous p=0.264, arterio-venous difference 0.375) between the groups, but there were differences in EMPs (p=0.049), vWf (p=0.004) and sEsel (p=0.032). In the entire cohort, and in diabetes alone, EMPs correlated with venous oxygenation (r=0.24, p=0.009 and r=0.43, p=0.011 respectively), while in DM+CVD, sEsel correlated with venous oxygenation (r=0.55, p=0.002) and with the arterial-venous difference (r=-0.63, p=0.001). In multivariate regression analysis of vascular markers against retinal oximetry indices in the entire group, EMPs were positively linked to venous oxygenation (p=0.037). Despite differences in systemic markers of vascular function between DM, CVD and DM+CVD, there was no difference in arterial or venous retinal oxygenation, or their difference. However, EMPs were linked to venous oximetry, and may provide further insight into the mechanisms underlying diabetes and diabetic retinopathy.

Adipocyte-specific ablation of the Ca2+ pump SERCA2 impairs whole-body metabolic function and reveals the diverse metabolic flexibility of white and brown adipose tissue

ObjectiveSarco/endoplasmic reticulum Ca2+-ATPase (SERCA) transports Ca2+ from the cytosol into the endoplasmic retitculum (ER) and is essential for appropriate regulation of intracellular Ca2+ homeostasis. The objective of this study was to test the hypothesis that SERCA pumps are involved in the regulation of white adipocyte hormone secretion and other aspects of adipose tissue function and that this control is disturbed in obesity-induced type-2 diabetes. MethodsSERCA expression was measured in isolated human and mouse adipocytes as well as in whole mouse adipose tissue by Western blot and RT-qPCR. To test the significance of SERCA2 in adipocyte functionality and whole-body metabolism, we generated adipocyte-specific SERCA2 knockout mice. The mice were metabolically phenotyped by glucose tolerance and tracer studies, histological analyses, measurements of glucose-stimulated insulin release in isolated islets, and gene/protein expression analyses. We also tested the effect of pharmacological SERCA inhibition and genetic SERCA2 ablation in cultured adipocytes. Intracellular and mitochondrial Ca2+ levels were recorded with dual-wavelength ratio imaging and mitochondrial function was assessed by Seahorse technology. ResultsWe demonstrate that SERCA2 is downregulated in white adipocytes from patients with obesity and type-2 diabetes as well as in adipocytes from diet-induced obese mice. SERCA2-ablated adipocytes display disturbed Ca2+ homeostasis associated with upregulated ER stress markers and impaired hormone release. These adipocyte alterations are linked to mild lipodystrophy, reduced adiponectin levels, and impaired glucose tolerance. Interestingly, adipocyte-specific SERCA2 ablation leads to increased glucose uptake in white adipose tissue while the glucose uptake is reduced in brown adipose tissue. This dichotomous effect on glucose uptake is due to differently regulated mitochondrial function. In white adipocytes, SERCA2 deficiency triggers an adaptive increase in fibroblast growth factor 21 (FGF21), increased mitochondrial uncoupling protein 1 (UCP1) levels, and increased oxygen consumption rate (OCR). In contrast, brown SERCA2 null adipocytes display reduced OCR despite increased mitochondrial content and UCP1 levels compared to wild type controls. ConclusionsOur data suggest causal links between reduced white adipocyte SERCA2 levels, deranged adipocyte Ca2+ homeostasis, adipose tissue dysfunction and type-2 diabetes.