Time Course of Diffusion Kurtosis in Cerebral Infarctions of Transient Middle Cerebral Artery Occlusion Rat Model.

OBJECTIVE: To evaluate the relationship between fiber bundle direction and changes in diffusion kurtosis, we evaluated the apparent diffusion kurtosis coefficients (AKCs) that were perpendicular to and parallel to the principal diffusion tensor eigenvector. MATERIALS AND METHODS: Adult male Wistar rats were subjected to 30 or 60 minutes of middle cerebral artery occlusion and imaged with a 7T Magnetic Resonance Imager System (Varian MRI System 7T/210: Agilent Technologies, CA). Diffusion kurtosis images were obtained before middle cerebral artery (MCA) reperfusion and 3, 6, and 24 hours after reperfusion to generate the apparent diffusion coefficient (ADC), fractional anisotropy (FA), mean apparent diffusion kurtosis coefficient (mAKC), AKC axial to the eigenvector (axAKC), and AKC radial to the eigenvector (radAKC) images. The time course of the region/normal ratio was evaluated for the above parameters in the caudoputamen and white matter. RESULTS: Relative FA and relative ADC values decreased 3 hours after MCA reperfusion and remained decreased until 24 hours. Relative mAKC, axAKC, and radAKC values were increased 3 hours after MCA reperfusion, peaked after 6 hours, and slightly decreased after 24 hours. In the white matter, axAKC showed larger changes than radAKC. CONCLUSION: The time course of the diffusion kurtosis value showed earlier pseudonormalization than the ADC value of the lesions. For white matter lesions, the increase in axAKC was larger than that in radAKC, suggesting that the tissue changes after infarction mainly produce reduced diffusivity along the fibers and lead to increased inhomogeneity of the diffusion.

Non-Gaussian diffusion-weighted imaging for assessing diurnal changes in intervertebral disc microstructure.

PURPOSE: To investigate the use of non-Gaussian diffusion-weighted imaging (q-space imaging [QSI]) to estimate diurnal changes in intervertebral disc (IVD) microstructure. MATERIALS AND METHODS: IVDs of 15 male subjects (mean age, 27.3 years; mean body mass index, 22.50 kg/m(2) ) were investigated once in the morning, less than 30 min after rising, and a second time in the evening after at least 10 h of normal physical activity, using 3 Tesla (T) MR imaging. T2 mapping and QSI data values (apparent diffusion coefficient [ADC], root mean square displacement [RMSD], and apparent kurtosis coefficient [AKC]) were calculated and compared between the morning and evening imaging sessions. RESULTS: The T2, ADC, and RMSD values showed a significant decrease in the evening (175.8 ± 49.5 ms, 1.56 ± 0.32 10(-3) mm(2) /s and 40.0 ± 3.0 µm, respectively; P < 0.05 for all values; paired t-test), when compared with the morning values (226.5 ± 83.8 ms, 1.69 ± 0.29 10(-3) mm(2) /s and 45.2 ± 2.9 µm, respectively). The AKC value showed a significant increase in the evening (0.67 ± 0.08), when compared with the morning value (0.58 ± 0.04; P < 0.05). CONCLUSION: The RMSD and AKC values obtained from QSI analysis may be biomarkers for IVD diurnal microstructural changes.

Corticospinal tract-sparing intensity-modulated radiotherapy treatment planning.

AIM: To establish intensity-modulated radiotherapy (IMRT) planning procedures that spare the corticospinal tract by integrating diffusion tensor tractography into the treatment planning software. BACKGROUND: Organs at risk are generally contoured according to the outline of the organ as demonstrated by CT or MRI. But a part of the organ with specific function is difficult to protect, because such functional part of the organ cannot be delineated on CT or conventional sequence of MRI. METHODS: Diagnostic and treatment planning images of glioblastoma patients who had been treated by conventional 3-dimensional conformal radiotherapy were used for re-planning of IMRT. Three-dimensional fiber maps of the corticospinal tracts were created from the diffusion tensors obtained from the patients before the surgery, and were blended with the anatomical MR images (i.e. gadolinium-enhanced T1-weighted images or T2-weighted images). DICOM-formatted blended images were transferred and fused to the planning CT images. Then, IMRT plans were attempted. RESULTS: The corticospinal tracts could be contoured as organs at risk (OARs), because the blended images contained both anatomical information and fiber-tract maps. Other OARs were contoured in a way similar to that of ordinary IMRT planning. Gross tumor volumes, clinical target volumes, planning target volumes, and other OARs were contoured on the treatment planning software, and IMRT plans were made. CONCLUSIONS: IMRT plans with diminished doses to the corticospinal tract were attained. This technique enabled us to spare specific neuron fibers as OARs which were formerly "invisible" and to reduce the probability of late morbidities.

Microstructural changes of the corticospinal tract in idiopathic normal pressure hydrocephalus: a comparison of diffusion tensor and diffusional kurtosis imaging.

INTRODUCTION: The goals of this study were to examine the usefulness of diffusional kurtosis imaging (DKI) for assessing microstructural changes in the compressed corticospinal tract (CST) among patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: Eleven patients with iNPH (mean age: 73.6 years, range: 65-84), who underwent 3-T magnetic resonance imaging, including DKI before surgery, were recruited. Six age-matched, healthy subjects (mean age: 69.8 years, range: 60-75) served as the control group. DKI and diffusion tensor imaging parameters were calculated and compared between the iNPH and the control groups using tract-specific analysis of the CST at the level of the lateral ventricle. RESULTS: Mean diffusional kurtosis (DK) and axial diffusion kurtosis were significantly lower in iNPH patients. However, apparent diffusion coefficient, fractional anisotropy, and axial eigenvalue (λ1) were significantly higher in the iNPH group than in the control group. CONCLUSIONS: The mechanical pressure caused by ventricular enlargement in iNPH patients might induce formation of well-aligned fiber tracts and increased fiber density in the CST, resulting in decreased DK. DKI is able to depict both the altered microstructure and water molecule movement within neural axons and intra- or extracellular space. In addition, the investigated DKI parameters provide different information about white matter relative to conventional diffusional metrics for iNPH.

New diffusion metrics for spondylotic myelopathy at an early clinical stage.

OBJECTIVES: To investigate the use of root mean square displacement (RMSD) and mean diffusional kurtosis (DK) metrics of q-space imaging data to estimate spinal cord compression in patients with early cervical spondylosis. METHODS: We studied 50 consecutive patients at our institution (22 male, 28 female; mean age 58 years; age range 20-86 years) who had clinical signs and symptoms suggestive of early clinical stage cervical myelopathy. After conventional magnetic resonance (MR) imaging, diffusion tensor and q-space image data were acquired using 3-T MR imaging. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), RMSD and mean DK values were calculated and compared between compressed and uncompressed spinal cords. RESULTS: FA and mean DK values were significantly lower and RMSD was significantly higher (P = 0.0060, 0.0020 and 0.0062, respectively; Mann-Whitney U test with the Bonferroni correction) in compressed spinal cords than in uncompressed cords. ADC was also higher in compressed cords, but this difference was not statistically significant. CONCLUSIONS: In the evaluation of spinal cord damage in early cervical spondylosis, mean DK and RMSD values in the spinal cord may be highly sensitive indicators of microstructural change and damage. KEY POINTS: • Absolute surgical indications for cervical spondylosis with myelopathy remain to be established. • Diffusion tensor MRI shows abnormalities in normal-appearing but compressed spinal cord. • Non-Gaussian diffusion analysis is highly sensitive in revealing spinal cord damage.

Tract-specific analysis of white matter integrity disruption in schizophrenia.

Several studies have suggested that white matter integrity is disrupted in some brain regions in patients with schizophrenia. The purpose of this study was to assess the white matter integrity of the cingulum, uncinate fasciculus, fornix, and corpus callosum using diffusion tensor imaging (DTI). Participants comprised 39 patients with schizophrenia (19 males and 20 females) and 40 age-matched normal controls (20 males and 20 females). We quantitatively assessed the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of the anterior cingulum, body of the cingulum, uncinate fasciculus, fornix, and corpus callosum on a tract-specific basis using diffusion tensor tractography (DTT). Group differences in FA and ADC between the patients and normal controls were sought. Additional exploratory analyses of the relationship between the FA or ADC and four clinical parameters (i.e., illness duration, positive symptom scores, negative symptom scores, and medication dosage) were performed. Results were analyzed in gender-combined and gender-separated group comparisons. FA was significantly lower on both sides of the anterior cingulum, uncinate fasciculus, and fornix in the schizophrenia patients irrespective of gender group separation. In the gender-combined analyses, significantly higher ADC values were demonstrated in the schizophrenia patients in both sides of the anterior cingulum, body of the cingulum and uncinate fasciculus, the left fornix, and the corpus callosum, compared with those of the normal controls. In the gender-separated analyses, the male patients showed higher ADC in the left anterior cingulum, the bilateral cingulum bodies, and the bilateral uncinate fasciculi. The female patients showed higher ADC in the right anterior cingulum, the left fornix, and the bilateral uncinate fasciculus. In correlation analyses, a significant negative correlation was found between illness duration and ADC in the right anterior cingulum in the gender-combined analyses. The gender-separated analyses found that the male patients had a significant negative correlation between negative symptom scores and FA in the right fornix, a positive correlation between illness duration and FA in the right anterior cingulum, and a negative correlation between illness duration and FA in the left uncinate fasciculus. Our DTI study showed that the integrity of white matter is disrupted in patients with schizophrenia. The results of our sub-analyses suggest that changes in FA and ADC may be related to negative symptom scores or illness duration.

Recent Advances in Parameter Inference for Diffusion MRI Signal Models.

In this paper, fundamentals and recent progress for obtaining biological features quantitatively by using diffusion MRI are reviewed. First, a brief description of diffusion MRI history, application, and development was presented. Then, well-known parametric models including diffusion tensor imaging (DTI), diffusional kurtosis imaging (DKI), and neurite orientation dispersion diffusion imaging (NODDI) are introduced with several classifications in various viewpoints with other modeling schemes. In addition, this review covers mathematical generalization and examples of methodologies for the model parameter inference from conventional fitting to recent machine learning approaches, which is called Q-space learning (QSL). Finally, future perspectives on diffusion MRI parameter inference are discussed with the aspects of imaging modeling and simulation.

[Evaluation of Diffusional Kurtosis Inference Using Synthetic q-space Learning and Bias Correction].

PURPOSE: In synthetic q-space learning (synQSL), which uses deep learning to infer the diffusional kurtosis (K), a bias that depends on the noise level added to the synthetic training data occurs. The purpose of this study was to evaluate K inference using synQSL and bias correction. METHODS: Using the synthetic test data and the real image data, K was inferred by synQSL, and bias correction was performed. Then, those results were compared with K inferred by fitting by the least-squares fitting (LSF) method. At this time, the noise level of the training data was set to 3 types, the noise level of the synthesis test data was set to 5 types, and the number of excitation (NEX) of the real image data was set to 4 types. Robustness of inference was evaluated by the outlier rate, which is the ratio of K outliers to the whole brain. We also evaluated the root mean square error (RMSE) of the inferred K. RESULTS: The outlier rate inferred by synQSL without correction was significantly lower in the test data of each noise level than that by the LSF method and was further reduced by correction. In addition, the RMSE of NEX 1 with NEX 4 as the correct answer based on the real image data had the smallest correction result of K by synQSL. CONCLUSION: Inferring K using synQSL and bias correction is a robust and small error method compared to that using the LSF method.

Advantages of Using Both Voxel- and Surface-based Morphometry in Cortical Morphology Analysis: A Review of Various Applications.

Surface-based morphometry (SBM) is extremely useful for estimating the indices of cortical morphology, such as volume, thickness, area, and gyrification, whereas voxel-based morphometry (VBM) is a typical method of gray matter (GM) volumetry that includes cortex measurement. In cases where SBM is used to estimate cortical morphology, it remains controversial as to whether VBM should be used in addition to estimate GM volume. Therefore, this review has two main goals. First, we summarize the differences between the two methods regarding preprocessing, statistical analysis, and reliability. Second, we review studies that estimate cortical morphological changes using VBM and/or SBM and discuss whether using VBM in conjunction with SBM produces additional values. We found cases in which detection of morphological change in either VBM or SBM was superior, and others that showed equivalent performance between the two methods. Therefore, we concluded that using VBM and SBM together can help researchers and clinicians obtain a better understanding of normal neurobiological processes of the brain. Moreover, the use of both methods may improve the accuracy of the detection of morphological changes when comparing the data of patients and controls.In addition, we introduce two other recent methods as future directions for estimating cortical morphological changes: a multi-modal parcellation method using structural and functional images, and a synthetic segmentation method using multi-contrast images (such as T1- and proton density-weighted images).

Temporal Progression Patterns of Brain Atrophy in Corticobasal Syndrome and Progressive Supranuclear Palsy Revealed by Subtype and Stage Inference (SuStaIn).

Differentiating corticobasal degeneration presenting with corticobasal syndrome (CBD-CBS) from progressive supranuclear palsy with Richardson's syndrome (PSP-RS), particularly in early stages, is often challenging because the neurodegenerative conditions closely overlap in terms of clinical presentation and pathology. Although volumetry using brain magnetic resonance imaging (MRI) has been studied in patients with CBS and PSP-RS, studies assessing the progression of brain atrophy are limited. Therefore, we aimed to reveal the difference in the temporal progression patterns of brain atrophy between patients with CBS and those with PSP-RS purely based on cross-sectional data using Subtype and Stage Inference (SuStaIn)-a novel, unsupervised machine learning technique that integrates clustering and disease progression modeling. We applied SuStaIn to the cross-sectional regional brain volumes of 25 patients with CBS, 39 patients with typical PSP-RS, and 50 healthy controls to estimate the two disease subtypes and trajectories of CBS and PSP-RS, which have distinct atrophy patterns. The progression model and classification accuracy of CBS and PSP-RS were compared with those of previous studies to evaluate the performance of SuStaIn. SuStaIn identified distinct temporal progression patterns of brain atrophy for CBS and PSP-RS, which were largely consistent with previous evidence, with high reproducibility (99.7%) under cross-validation. We classified these diseases with high accuracy (0.875) and sensitivity (0.680 and 1.000, respectively) based on cross-sectional structural brain MRI data; the accuracy was higher than that reported in previous studies. Moreover, SuStaIn stage correctly reflected disease severity without the label of disease stage, such as disease duration. Furthermore, SuStaIn also showed the genialized performance of differentiation and reflection for CBS and PSP-RS. Thus, SuStaIn has potential for improving our understanding of disease mechanisms, accurately stratifying patients, and providing prognoses for patients with CBS and PSP-RS.

Integrated lymphography using fluorescence imaging and magnetic resonance imaging in intact mice.

We assessed lymph drainage in living mice by an integrated imaging method using fluorescence imaging (FLI) and magnetic resonance imaging (MRI). Mice were subcutaneously injected with quantum dots and gadofluorine 8 into the right rear footpad. They were fixed on a transparent flat plate and underwent FLI and MRI successively. Small markers were attached to the mouse surface for spatial coregistration, and image fusion of FLIs and MRIs was performed. Two-dimensional fluorescence reflectance imaging was used for FLI. FLI and MRI provided generally consistent results and demonstrated lymphatic flow to the popliteal, sacral, and iliac lymph nodes in most mice and to the renal, inguinal, and lumbar-aortic lymph nodes in some mice. On the fusion images, the locations of the lymph nodes in the mouse trunk were in good agreement between FLI and MRI, indicating successful spatial registration even for the deep structures. The popliteal node tended to be visualized a little farther caudally in FLI than in MRI, presumably because the overlying tissues were thicker in the cranial portion. Integrated FLI/MRI lymphography with image fusion appears to be a useful tool for analysis of the murine lymphatic system.

Prospective Study of Spatial Distribution of Missed Lung Nodules by Readers in CT Lung Screening Using Computer-assisted Detection.

PURPOSE: To evaluate the spatial patterns of missed lung nodules in a real-life routine screening environment. MATERIALS AND METHODS: In a screening institute, 4,822 consecutive adults underwent chest CT, and each image set was independently interpreted by two radiologists in three steps: (1) independently interpreted without computer-assisted detection (CAD) software, (2) independently referred to the CAD results, (3) determined by the consensus of the two radiologists. The locations of nodules and the detection performance data were semi-automatically collected using a CAD server integrated into the reporting system. Fisher's exact test was employed for evaluating findings in different lung divisions. Probability maps were drawn to illustrate the spatial distribution of radiologists' missed nodules. RESULTS: Radiologists significantly tended to miss lung nodules in the bilateral hilar divisions (p < 0.01). Some radiologists had their own spatial pattern of missed lung nodules. CONCLUSION: Radiologists tend to miss lung nodules present in the hilar regions significantly more often than in the rest of the lung.

Formation of long-term memory representation in human temporal cortex related to pictorial paired associates.

It is widely held that long-term memory gradually develops in the temporal neocortex after initial memory encoding into the hippocampus. However, little is known as to whether and where long-term memory can be newly created in the human temporal neocortex. In this functional magnetic resonance imaging study, we detected brain activity in the temporal neocortex that was developed approximately 8 weeks after study of unfamiliar pictorial paired associates. Two sets of paired Fourier figures were studied, one approximately 8 weeks before test and the other immediately before test, keeping the correct performance during the tests balanced across the two sets of stimuli. Significant signal increase was observed in the right hippocampus during retrieval of newly studied pairs relative to initially studied pairs. In contrast, significant signal increase was observed in the anterior temporal cortex during retrieval of initially studied pairs relative to newly studied pairs. The greater activity during retrieval of older memory developed in the temporal neocortex provides direct evidence of formation of temporal neocortical representation for stable long-term memory.

Integrated imaging approach to tumor model mice using bioluminescence imaging and magnetic resonance imaging.

We developed an integrated imaging method using bioluminescence imaging (BLI) and magnetic resonance imaging (MRI) and applied it to mouse tumor monitoring. BLIs and MRIs were successively acquired from mice fixed on a transparent flat plate and were registered using three small markers. After spatial coregistration, the two-dimensional BLI was fused with all MRI slices. The accuracy of image registration was evaluated using fluorescence imaging and MRI of many markers attached to the mice. Mice were inoculated with luciferase-expressing tumor cells subcutaneously or directly into the liver, and disease progression was evaluated repeatedly by integrated BLI-MRI. Image registration was achieved with acceptable accuracy, although the registration error increased with increasing distance from the center of the imaging field and was larger in imaging the convex dorsal side of the mouse than in imaging the flat ventral side. Integrated BLI-MRI allowed longitudinal assessment of disease progression and appeared to facilitate detailed interpretation of the imaging findings. It aided the anatomic localization of lesions demonstrated by BLI and recognition of MRI abnormalities corresponding to BLI foci. Integrated BLI-MRI is feasible and appears to be a practical method for comprehensive, longitudinal assessment of disease model mice.

Sex dimorphism in gray/white matter volume and diffusion tensor during normal aging.

The purpose of this study is to elucidate sex differences in global and regional gray/white matter volume, mean diffusivity (MD), and fractional anisotropy (FA) during normal aging using voxel-based analysis. We studied 245 healthy right-handed subjects with a wide range of ages (115 women, 22-70 years; 130 men, 21-71 years). Regarding global effects, inclusion of a quadratic age term improved the fit to data for white matter fraction and MD, but not for global gray matter volume/fraction or FA. Regarding regional effects, we found anterior-dominant volume loss, FA decrease predominantly in the anterior white matter, and MD increase predominantly in perisylvian regions and periventricular white matter against age for both sexes. Compared with women, we found a steeper FA decline for men in the right inferior fronto-temporal areas, extending to the anterior cingulate cortex, and an accelerated MD increase for men in the bilateral frontal, temporal, and parietal areas. There was no area in which interaction of sex with age was significant for regional volume, or in which a steeper FA decline or accelerated MD increase for women was significant. Our results provide strong evidence of sex dimorphism in global and focal diffusion characteristics during normal aging.

Age-related changes in regional brain volume evaluated by atlas-based method.

INTRODUCTION: The effects of aging on brain volume are generally investigated using voxel-based morphometry (VBM) or the manually traced region-of-interest (ROI) method. We introduce an atlas-based method as a methodological alternative that calculates absolute volume as a non-biased and semi-automatic whole-brain technique. METHODS: We enrolled 115 healthy females (mean age, 36.7 years) and 130 healthy males (mean age, 37.1 years). Volume data were acquired using a 1.5 tesla magnetic resonance scanner. After spatial normalization, a lobar-based atlas template was applied, and the absolute volumes of the frontal, temporal, parietal, and occipital lobes and the sublobar and limbic areas were calculated bilaterally. The effects of age on regional brain volume were evaluated statistically. RESULTS: The volume of all ROIs declined linearly with increasing age. The bilateral frontal lobes showed the steepest involution. Analysis of variance revealed significant laterality and interaction of gender and age. CONCLUSION: The atlas-based method introduced in the present study has advantages over the manually traced ROI method in its objectivity, coverage, and time requirement and has an advantage over the VBM method in its computability of absolute volume. The results are largely in agreement with those reported previously, thereby reconfirming the importance of matching gender and age in analyzing brain disorders.

Diffusion tensor tract-specific analysis of the uncinate fasciculus in patients with amyotrophic lateral sclerosis.

INTRODUCTION: The uncinate fasciculus (UF) consists of core fibers connecting the frontal and temporal lobes and is considered to be related to cognitive/behavioral function. Using diffusion tensor tractography, we quantitatively evaluated changes in fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) of the UF by tract-specific analysis to evaluate the damage of the UF in patients with amyotrophic lateral sclerosis (ALS). METHODS: We obtained diffusion tensor images of 15 patients with ALS and 9 age-matched volunteers. RESULTS: Patients with ALS showed significantly lower mean FA (P = 0.029) compared with controls. No significant difference was seen in mean ADC. CONCLUSION: The results suggest that damage of the UF in patients with ALS can be quantitatively evaluated with FA.

Voxel-based analyses of gray/white matter volume and diffusion tensor data in major depression.

The purpose of this study is to use voxel-based analysis to simultaneously elucidate regional changes in gray/white matter volume, mean diffusivity (MD), and fractional anisotropy (FA) in patients with unipolar major depressive disorder. We studied 21 right-handed patients and 42 age- and gender-matched right-handed normal subjects. Local areas showing significant gray matter volume reduction in depressive patients compared with controls were observed in the right parahippocampal gyrus, hippocampus, bilateral middle frontal gyri, bilateral anterior cingulate cortices, left parietal and occipital lobes, and right superior temporal gyrus. Local areas showing an increase of MD in depressive patients were observed in the bilateral parahippocampal gyri, hippocampus, pons, cerebellum, left frontal and temporal lobes, and right frontal lobe. There was no significant difference between the two groups for FA and white matter volume in the entire brain. Although there was no local area where brain volume and MD were significantly correlated with disease severity, FA tended to correlate negatively with total days depressed in the right anterior cingulate and the left frontal white matter. These results suggest that the frontolimbic neural circuit might play an important role in the neuropathology of patients with major depressive disorder.

Automated segmentation method for spinal column based on a dual elliptic column model and its application for virtual spinal straightening.

Segmentation of vertebral bones in computed tomographic data is important as a first stage of image-based radiological tasks. However, it is a challenging problem to segment an affected spine correctly. In this study, we propose a new method of segmentation of thoracic and lumbar vertebral bodies from thin-slice computed tomographic images. Especially, we focus on a deformable model-based segmentation scheme to confirm the feasibility in clinical data sets with various bone diseases, such as bone metastases and scoliosis. As an application of this algorithm, virtual straightening of the thoracolumbar spine is also performed. Results on a database of 16 patients indicate the applicability of our method to spines affected by scoliosis and multiple bone metastases.

Novel platform for development, training, and validation of computer-assisted detection/diagnosis software.

PURPOSE: To build a novel, open-source, purely web-based platform system to address problems in the development and clinical use of computer-assisted detection/diagnosis (CAD) software. The new platform system will replace the existing system for the development and validation of CAD software, Clinical Infrastructure for Radiologic Computation of United Solutions (CIRCUS). METHODS: In our new system, the two top-level applications visible to users are the web-based image database (CIRCUS DB; database) and the Docker plug-in-based CAD execution platform (CIRCUS CS; clinical server). These applications are built on top of a shared application programming interface server, a three-dimensional image viewer component, and an image repository. RESULTS: We successfully installed our new system into a Linux server at two clinical sites. A total of 1954 cases were registered in CIRCUS DB. We have been utilizing CIRCUS CS with four Docker-based CAD plug-ins. CONCLUSIONS: We have successfully built a new version of the CIRCUS system. Our platform was successfully implemented at two clinical sites, and we plan to publish it as an open-source software project.