MRI index of glymphatic system mediates the influence of locus coeruleus on cognition in Parkinson's disease.

INTRODUCTION: Although locus coeruleus (LC) has been demonstrated to play a critical role in the cognitive function of Parkinson's disease (PD), the underlying mechanism has not been elucidated. The objective was to investigate the relationship among LC degeneration, cognitive performance, and the glymphatic function in PD. METHODS: In this retrospective study, 71 PD subjects (21 with normal cognition; 29 with cognitive impairment (PD-MCI); 21 with dementia (PDD)) and 26 healthy controls were included. All participants underwent neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and diffusion tensor image scanning on a 3.0 T scanner. The brain glymphatic function was measured using diffusion along the perivascular space (ALPS) index, while LC degeneration was estimated using the NM contrast-to-noise ratio of LC (CNRLC). RESULTS: The ALPS index was significantly lower in both the whole PD group (P = 0.04) and the PDD subgroup (P = 0.02) when compared to the controls. Similarly, the CNRLC was lower in the whole PD group (P < 0.001) compared to the controls. In the PD group, a positive correlation was found between the ALPS index and both the Montreal Cognitive Assessment (MoCA) score (r = 0.36; P = 0.002) and CNRLC (r = 0.26; P = 0.03). Mediation analysis demonstrated that the ALPS index acted as a significant mediator between CNRLC and the MoCA score in PD subjects. CONCLUSION: The ALPS index, a neuroimaging marker of glymphatic function, serves as a mediator between LC degeneration and cognitive function in PD.

Phase Retrieval-Based Phase-Contrast Imaging and CT of Living Zebrafish.

Zebrafish are widely used as experimental animal models. They are small and move fast in the water. Real-time imaging of fast-moving zebrafish is a challenge, and it requires that the imaging technique has higher spatiotemporal resolution and penetration ability. The purpose of this study was to evaluate the feasibility of dynamic phase retrieval (PR)-based phase-contrast imaging (PCI) for real-time displaying of the breathing and swimming process in unanesthetized free-moving zebrafish, and to evaluate the feasibility of PR-based phase-contrast CT (PCCT) for visualizing the soft tissues in anesthetized living zebrafish. PR was performed using the phase-attenuation duality (PAD) method with the δ/ß values (PAD property) of 100 and 1000 for dynamic PR-based PCI and PR-based PCCT, respectively. The contrast-to-noise ratio (CNR) was used for quantitatively assessing the visibility of the adipose tissue and muscle tissue. The skeleton and swim bladder chambers in fast-moving zebrafish were clearly shown. The dynamic processes of breathing and swimming were visibly recorded. The respiratory intensity and frequency and the movement flexibility of the zebrafish could be dynamically evaluated. By producing more obvious image contrast, PR-based PCCT clearly showed the adipose tissue and muscle tissue. The CNRs from PR-based PCCT were significantly higher than those from PR-free PCCT for both adipose tissue (9.256 ± 2.037 vs. 0.429 ± 0.426, p < 0.0001) and muscle tissue (7.095 ± 1.443 vs. 0.324 ± 0.267, p < 0.0001). Dynamic PR-based PCI holds the potential for investigating both morphological abnormalities and motor disorders. PR-based PCCT offers clear visualization and the potential for quantification of soft tissues in living zebrafish.

Diagnosing Parkinson's disease by combining neuromelanin and iron imaging features using an automated midbrain template approach.

BACKGROUND AND PURPOSE: Early diagnosis of Parkinson's disease (PD) is still a clinical challenge. Most previous studies using manual or semi-automated methods for segmenting the substantia nigra (SN) are time-consuming and, despite raters being well-trained, individual variation can be significant. In this study, we used a template-based, automatic, SN subregion segmentation pipeline to detect the neuromelanin (NM) and iron features in the SN and SN pars compacta (SNpc) derived from a single 3D magnetization transfer contrast (MTC) gradient echo (GRE) sequence in an attempt to develop a comprehensive imaging biomarker that could be used to diagnose PD. MATERIALS AND METHODS: A total of 100 PD patients and 100 age- and sex-matched healthy controls (HCs) were imaged on a 3T scanner. NM-based SN (SNNM) boundaries and iron-based SN (SNQSM) boundaries and their overlap region (representing the SNpc) were delineated automatically using a template-based SN subregion segmentation approach based on quantitative susceptibility mapping (QSM) and NM images derived from the same MTC-GRE sequence. All PD and HC subjects were evaluated for the nigrosome-1 (N1) sign by two raters independently. Receiver Operating Characteristic (ROC) analyses were performed to evaluate the utility of SNNM volume, SNQSM volume, SNpc volume and iron content with a variety of thresholds as well as the N1 sign in diagnosing PD. Correlation analyses were performed to study the relationship between these imaging measures and the clinical scales in PD. RESULTS: In this study, we verified the value of the fully automatic template based midbrain deep gray matter mapping approach in differentiating PD patients from HCs. The automatic segmentation of the SN in PD patients led to satisfactory DICE similarity coefficients and volume ratio (VR) values of 0.81 and 1.17 for the SNNM, and 0.87 and 1.05 for the SNQSM, respectively. For the HC group, the average DICE similarity coefficients and VR values were 0.85 and 0.94 for the SNNM, and 0.87 and 0.96 for the SNQSM, respectively. The SNQSM volume tended to decrease with age for both the PD and HC groups but was more severe for the PD group. For diagnosing PD, the N1 sign performed reasonably well by itself (Area Under the Curve (AUC) = 0.783). However, combining the N1 sign with the other quantitative measures (SNNM volume, SNQSM volume, SNpc volume and iron content) resulted in an improved diagnosis of PD with an AUC as high as 0.947 (using an SN threshold of 50ppb and an NM threshold of 0.15). Finally, the SNQSM volume showed a negative correlation with the MDS-UPDRS III (R2 = 0.1, p = 0.036) and the Hoehn and Yahr scale (R2 = 0.04, p = 0.013) in PD patients. CONCLUSION: In summary, this fully automatic template based deep gray matter mapping approach performs well in the segmentation of the SN and its subregions for not only HCs but also PD patients with SN degeneration. The combination of the N1 sign with other quantitative measures (SNNM volume, SNQSM volume, SNpc volume and iron content) resulted in an AUC of 0.947 and provided a comprehensive set of imaging biomarkers that, potentially, could be used to diagnose PD clinically.

Effect of gadopentetate dimeglumine on bone growth in zebrafish caudal fins.

Compared with MR plain scanning, gadolinium (Gd)-enhanced MR scanning can provide more diagnostic information. Gadopentetate dimeglumine is generally used as an MR enhancement contrast agent in some countries. It is a member of linear Gd-based contrast agents (GBCAs) which are considered more likely to release free Gd ions (Gd3+) than macrocyclic GBCAs. Gd3+ is one of the most effective known calcium antagonists, and can compete with calcium ions (Ca2+) in Ca2+-related biological reactions. In this study, animal models of tissue regeneration were established by cutting the caudal fins of zebrafish, and the models were exposed with gadopentetate dimeglumine solution for different immersion times of 1, 3, and 5 min. Three GBCA exposures per week were performed in the first 3 weeks of the follow-up time. Morphological parameters such as regenerative area (RA), bone density, bone thickness and regenerative bone volume (RBV) were quantified using a camera and synchrotron radiation micro CT. RA decreased as total Gd intake increased in both the female group (ρ = -0.784, P < 0.0001) and the male group (ρ = -0.471, P = 0.011). The bone density of the regenerated bone increased after Gd exposure in the treated groups. The morphology of the regenerated bone from the treated groups became shorter and thicker. Our results showed that gadopentetate dimeglumine had osteogenic toxicity in zebrafish.

Visualizing the deep cerebellar nuclei using quantitative susceptibility mapping: An application in healthy controls, Parkinson's disease patients and essential tremor patients.

The visualization and identification of the deep cerebellar nuclei (DCN) (dentate [DN], interposed [IN] and fastigial nuclei [FN]) are particularly challenging. We aimed to visualize the DCN using quantitative susceptibility mapping (QSM), predict the contrast differences between QSM and T2* weighted imaging, and compare the DCN volume and susceptibility in movement disorder populations and healthy controls (HCs). Seventy-one Parkinson's disease (PD) patients, 39 essential tremor patients, and 80 HCs were enrolled. The PD patients were subdivided into tremor dominant (TD) and postural instability/gait difficulty (PIGD) groups. A 3D strategically acquired gradient echo MR imaging protocol was used for each subject to obtain the QSM data. Regions of interest were drawn manually on the QSM data to calculate the volume and susceptibility. Correlation analysis between the susceptibility and either age or volume was performed and the intergroup differences of the volume and magnetic susceptibility in all the DCN structures were evaluated. For the most part, all the DCN structures were clearly visualized on the QSM data. The susceptibility increased as a function of volume for both the HC group and disease groups in the DN and IN (p < .001) but not the FN (p = .74). Only the volume of the FN in the TD-PD group was higher than that in the HCs (p = .012), otherwise, the volume and susceptibility among these four groups did not differ significantly. In conclusion, QSM provides clear visualization of the DCN structures. The results for the volume and susceptibility of the DCN can be used as baseline references in future studies of movement disorders.

Automatic detection of neuromelanin and iron in the midbrain nuclei using a magnetic resonance imaging-based brain template.

Parkinson disease (PD) is a chronic progressive neurodegenerative disorder characterized pathologically by early loss of neuromelanin (NM) in the substantia nigra pars compacta (SNpc) and increased iron deposition in the substantia nigra (SN). Degeneration of the SN presents as a 50 to 70% loss of pigmented neurons in the ventral lateral tier of the SNpc at the onset of symptoms. Also, using magnetic resonance imaging (MRI), iron deposition and volume changes of the red nucleus (RN), and subthalamic nucleus (STN) have been reported to be associated with disease status and rate of progression. Further, the STN serves as an important target for deep brain stimulation treatment in advanced PD patients. Therefore, an accurate in-vivo delineation of the SN, its subregions and other midbrain structures such as the RN and STN could be useful to better study iron and NM changes in PD. Our goal was to use an MRI template to create an automatic midbrain deep gray matter nuclei segmentation approach based on iron and NM contrast derived from a single, multiecho magnetization transfer contrast gradient echo (MTC-GRE) imaging sequence. The short echo TE = 7.5 ms data from a 3D MTC-GRE sequence was used to find the NM-rich region, while the second echo TE = 15 ms was used to calculate the quantitative susceptibility map for 87 healthy subjects (mean age ± SD: 63.4 ± 6.2 years old, range: 45-81 years). From these data, we created both NM and iron templates and calculated the boundaries of each midbrain nucleus in template space, mapped these boundaries back to the original space and then fine-tuned the boundaries in the original space using a dynamic programming algorithm to match the details of each individual's NM and iron features. A dual mapping approach was used to improve the performance of the morphological mapping of the midbrain of any given individual to the template space. A threshold approach was used in the NM-rich region and susceptibility maps to optimize the DICE similarity coefficients and the volume ratios. The results for the NM of the SN as well as the iron containing SN, STN, and RN all indicate a strong agreement with manually drawn structures. The DICE similarity coefficients and volume ratios for these structures were 0.85, 0.87, 0.75, and 0.92 and 0.93, 0.95, 0.89, 1.05, respectively, before applying any threshold on the data. Using this fully automatic template-based deep gray matter mapping approach, it is possible to accurately measure the tissue properties such as volumes, iron content, and NM content of the midbrain nuclei.

Phase retrieval-based phase-contrast CT for vascular imaging with microbubble contrast agent.

PURPOSE: The introduction of microbubble contrast agent into tissues can create significant phase shifts. Phase retrieval (PR)-based phase-contrast computed tomography (PCCT) is an imaging method for retrieving and reconstructing the phase shifts within an object. This study aimed to evaluate the feasibility of PR-based PCCT with microbubble contrast agent for vascular imaging. METHODS: Projection phase-contrast images of individual microbubbles and a cluster of microbubbles were captured and compared. Contrast enhancement from microbubbles was evaluated by comparing to the gold standard iodine-based contrast agent in vitro. The arterial systems of 14 Sprague-Dawley rats were perfused with microbubbles or saline. The rat hearts and the arterial systems were excised and imaged ex vivo. CT imaging was performed at the energy of 22 keV. PR was performed using the phase-attenuation duality (PAD) method with different δ/ß values (PAD property). The contrast-to-noise ratio (CNR) was used for quantitatively assessing the contrast enhancement. RESULTS: Individual microbubbles functioned as a lens to focus the x rays, whereas, a cluster of microbubbles scattered the x rays. In the in vitro experiment, the contrast enhancement from iodine was significantly greater than that from microbubbles (P < 0.05). In the heart samples, the CNRs for microbubbles on PR-based PCCT were significantly greater than those on absorption-contrast CT (ACCT) and PR-free PCCT (both P < 0.001). The CNRs for microbubbles were also significantly greater than those for saline on PR-based PCCT in the samples (P < 0.001). Although they provided weaker contrast enhancement than that from iodine, microbubbles could still provide sufficient contrast enhancement to clearly show the 3D architecture of rat aortas and their main branches. CONCLUSION: The imaging modality can currently be used as a complement or alternative to absorption-based microCT for imaging vessels in biological samples.

Susceptibility and Volume Measures of the Mammillary Bodies Between Mild Cognitively Impaired Patients and Healthy Controls.

PURPOSE: To investigate the baseline values and differences for susceptibility and volume of the mammillary bodies between mild cognitively impaired (MCI) patients and healthy controls (HCs), and further explore their differences in relation to gender, MCI subtypes and apolipoprotein E (APOE) genotypes. METHODS: T1-weighted and multi-echo gradient echo imaging sequences were acquired on a 3T MR scanner to evaluate the T1W based volume and susceptibility differences in the mammillary body for 47 MCI and 47 HCs. T-tests were performed to compare volume and susceptibility between groups, and right and left hemispheres. Correlation analysis was used to relate the volume and mean susceptibility as a function of age in MCI and HC groups separately, and to investigate the relationship of susceptibility with the neuro-psychological scales in the MCI group. RESULTS: Susceptibility was found to be elevated within the right mammillary body in MCI patients compared to HCs (p < 0.05). There were no differences for the mammillary body volumes between the MCI and HC groups, although there was a reduction in volume with age for the MCI group (p = 0.007). Women showed decreased mammillary body volume compared to men in the HC group (p = 0.004). No significant differences were found in relation to MCI subtypes and APOE genotypes. No significant correlations were observed between mammillary body susceptibility with neuro-psychological scales. CONCLUSION: This work provides a quantitative baseline for both the volume and susceptibility of the mammillary body which can be used for future studies of cognitive impairment patients underlying the pathology of the Papez circuit.

Phase Contrast Imaging Based Microbubble Monitoring of Radiofrequency Ablation: An ex vivo Study.

BACKGROUND: To explore the potential of synchrotron radiation (SR) phase contrast imaging (PCI) for real-time microbubble formation monitoring during radiofrequency ablation (RFA). METHODS: RFA was performed on ex vivo porcine muscle tissue using unipolar and multi-tined expandable electrodes. Images of microbubble formation in the samples were captured by both SR PCI and absorption contrast imaging. The synchronous ablation temperature was recorded. Each RFA electrode type group contained 6 samples. Ablation size was assessed by histologic examination. RESULTS: Microbubble formation during RFA could be visualized by SR PCI. The diameter of the microbubbles revealed on the image ranged from tens of microns to several millimeters, and these microbubbles first appeared at the edge of the RFA electrode when the target region temperature reached approximately 60°C and rapidly extended outwards. The average microbubble range measured on PCI was 17.66 ± 0.74 mm. The average range of coagulation necrosis measured by histological examination was 17.22 ± 0.38 mm. There was no significant difference between them (P > 0.05). The range of microbubbles corresponded to the ablation zone. CONCLUSION: PCI enabled real-time high-resolution visualization of microbubble formation during RFA, indicating a potential for its use in ablation monitoring.

Impact of nasopharyngeal irradiation and gadolinium administration on changes in T1 signal intensity of the dentate nucleus in nasopharyngeal malignancy patients without intracranial abnormalities.

BACKGROUND: Irradiation has been found to increase T1 signal intensity (SI) of the dentate nucleus (DN) by accelerating the gadolinium deposition in patients after multiple gadolinium-based contrast agent (GBCA) administrations. Several reports have focused on this phenomenon in patients with brain tumors; however, data in patients receiving irradiation with no intracranial abnormalities (NIAs) are lacking. PURPOSE: To explore how nasopharyngeal irradiation affected SI changes on unenhanced T1 -weighted imaging (T1 WI) in the DN in nasopharyngeal malignancy (NPM) patients who presented with NIAs and who had multiple injection doses (IDs) of linear GBCAs. STUDY TYPE: Single-center, retrospective, case-control study. POPULATION: In all, 132 subjects: 66 NPM patients, 66 matched controls. FIELD STRENGTH/SEQUENCE: 1.5T and 3T/T1 WI, T2 WI, and fluid-attenuated inversion recovery (FLAIR). ASSESSMENT: Radiation doses (RDs) were calculated by a radiotherapy technician. SIs were measured by a radiologist. The DN-to-cerebellar white matter (CWM) SI ratios and their relative percentage change (Rchange ) were compared. STATISTICAL TESTS: Shapiro-Wilk test, paired t-test, independent t-test, Mann-Whitney U-test, Pearson and Spearman correlation. RESULTS: DN/CWM b ratios or R change from the NPM group were significantly higher than those from the control group (P < 0.001). No significant difference of DN/CWM a ratios was found between the two groups (P > 0.05). Positive correlations between R change , DN/CWM b ratio, and the number of IDs were found in both the NPM and control groups (P < 0.01). The overall changes of DN/CWM b ratio or R change between NPM and control groups were higher for the higher-IDs subgroup (≥10) than for the lower-IDs subgroup (<10). DATA CONCLUSION: Nasopharyngeal irradiation appeared to increase SI in T1 WI in NPM patients with NIAs and repeated GBCA administrations relative to control patients who also underwent GBCA administrations, especially when IDs ≥10. However, no significant association between R change and RDs to the DNs was found. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:250-259.

Imaging the Nigrosome 1 in the substantia nigra using susceptibility weighted imaging and quantitative susceptibility mapping: An application to Parkinson's disease.

Parkinson's disease (PD) is a clinically heterogeneous chronic progressive neuro-degenerative disease with loss of dopaminergic neurons in the nigrosome 1 (N1) territory of the substantia nigra pars compacta (SNpc). To date, there has been a major effort to identify changes in the N1 territory by monitoring increases of iron in the SNpc. However, there is no standard protocol being used to visualize or characterize the N1 territory. Therefore, the purpose of this study was to create a robust high quality, rapid imaging protocol, determine a slice by slice characterization of the appearance of N1 (the "N1 sign") and evaluate the loss of the N1 sign in order to differentiate healthy controls (HCs) from patients with PD. Firstly, one group of 10 HCs was used to determine the choice of imaging parameters. Secondly, another group of 80 HCs was used to characterize the appearance of the N1 sign and train the raters. In this step, the magnitude, susceptibility weighted images (SWI), quantitative susceptibility maps (QSM) and true SWI (tSWI) images were all reviewed using data from a 3D gradient recalled echo sequence. A resolution of 0.67 mm × 0.67 mm × 1.34 mm was chosen based on the ability to cover all the basal ganglia, midbrain and dentate nucleus with good signal-to-noise with echo times of 11 ms and 20 ms. Thirdly, 80 Parkinsonism and related disorders patients [idiopathic Parkinson's disease (IPD): 57; atypical parkinsonian syndromes (APs): 14; essential tremor (ET): 9] and one additional group of 80 age-matched HCs were blindly analyzed for the presence or absence of the N1 sign for a differential diagnosis. From the first group of 80 HCs, all of the 76 (100%) cases (4 were excluded due to motion artifacts) showed the N1 sign in one form or another after reviewing the first 5 caudal slices of the SN. For the second group of 80 HCs, 78 (97.5%) showed the N1 sign in at least 2 slices. Of the 80 Parkinsonism and related disorders patients, 32 (56.1%, 32/57) IPD and 6 (42.9%, 6/14) APs showed a bilateral loss of the N1 sign, 12 (21.1%, 12/57) IPD and 6 (42.9%, 6/14) APs showed the N1 sign unilaterally and 13 (22.8%, 13/57) IPD and 2 (14.2%, 2/14) APs showed the N1 sign bilaterally. Also, all 9 (100%, 9/9) ET patients showed the N1 sign bilaterally. The mean total structure and mean high susceptibility region for the SN for both IPD and APs patients with bilateral loss of N1 were higher than those of the HCs (p < 0.002). In conclusion, the N1 sign can be consistently visualized using tSWI with a resolution of at least 0.67 mm × 0.67 mm × 1.34 mm and can be seen in 95% of HCs.

Radiomic Features of the Nigrosome-1 Region of the Substantia Nigra: Using Quantitative Susceptibility Mapping to Assist the Diagnosis of Idiopathic Parkinson's Disease.

Introduction: The loss of nigrosome-1, which is also referred to as the swallow tail sign (STS) in T2*-weighted iron-sensitive magnetic resonance imaging (MRI), has recently emerged as a new biomarker for idiopathic Parkinson's disease (IPD). However, consistent recognition of the STS is difficult due to individual variations and different imaging parameters. Radiomics might have the potential to overcome these shortcomings. Therefore, we chose to explore whether radiomic features of nigrosome-1 of substantia nigra (SN) based on quantitative susceptibility mapping (QSM) could help to differentiate IPD patients from healthy controls (HCs). Methods: Three-dimensional multi-echo gradient-recalled echo images (0.86 × 0.86 × 1.00 mm3) were obtained at 3.0-T MRI for QSM in 87 IPD patients and 77 HCs. Regions of interest (ROIs) of the SN below the red nucleus were manually drawn on both sides, and subsequently, volumes of interest (VOIs) were segmented (these ROIs included four 1-mm slices). Then, 105 radiomic features (including 18 first-order features, 13 shape features, and 74 texture features) of bilateral VOIs in the two groups were extracted. Forty features were selected according to the ensemble feature selection method, which combined analysis of variance, random forest, and recursive feature elimination. The selected features were further utilized to distinguish IPD patients from HC using the SVM classifier with 10 rounds of 3-fold cross-validation. Finally, the representative features were analyzed using an unpaired t-test with Bonferroni correction and correlated with the UPDRS-III scores. Results: The classification results from SVM were as follows: area under curve (AUC): 0.96 ± 0.02; accuracy: 0.88 ± 0.03; sensitivity: 0.89 ± 0.06; and specificity: 0.87 ± 0.07. Five representative features were selected to show their detailed difference between IPD patients and HCs: 10th percentile and median in IPD patients were higher than those in HCs (all p < 0.00125), while Gray Level Run Length Matrix (GLRLM)-Long Run Low Gray Level Emphasis, Gray Level Size Zone Matrix (GLSZM)-Gray Level Non-Uniformity, and volume (all p < 0.00125) in IPD patients were lower than those in HCs. The 10th percentile was positively correlated with UPDRS-III score (r = 0.35, p = 0.001). Conclusion: Radiomic features of the nigrosome-1 region of SN based on QSM could be useful in the diagnosis of IPD and could serve as a surrogate marker for the STS.

Evaluating the effect of Avastin on breast cancer angiogenesis using synchrotron radiation.

BACKGROUND: The visualization of microvasculature is an essential step in understanding the mechanisms underlying early vessel disorders involved in breast cancer and for developing effective therapeutic strategies. However, generating detailed and reproducible data using immunohistochemistry analysis of breast cancer angiogenesis has been difficult. METHODS: To analyze the diversification of angiogenesis in the development of tumor growth and evaluate the anti-vascular effects of Avastin (bevacizumab), we used new X-ray microangiography and third-generation synchrotron radiation-based micro-computed tomography (SR micro-CT) technology. With these techniques, we were able to investigate the structures and density of microvessels in xenograft mouse models (n=24). Barium sulfate nanoparticles were injected into the left cardiac ventricle of the mice to allow the visualization of blood vessels. RESULTS: Three-dimensional structures of microvessels were displayed with a high spatial image resolution of 20-30 µm. The density of angiogenesis and the incidence of lung metastasis were significantly reduced in xenograft mouse models of breast cancer treated with Avastin compared with control groups. Also, the density of smaller vessels (diameter <50 µm) was significantly decreased in the Avastin-treated mice, while the density of larger vessels (diameter >100 µm) was not significantly changed. CONCLUSIONS: Avastin inhibited tumor growth and lung metastasis by reducing microvessels. Additionally, synchrotron radiation (SR) techniques are useful as an additional tool for more precise quantification of angiogenesis.

Microbubbles containing gadolinium as contrast agents for both phase contrast and magnetic resonance imaging.

Portal vein imaging is an important method for investigating portal venous disorders. However, the diagnostic requirements are not usually satisfied when using single imaging techniques. Diagnostic accuracy can be improved by combining different imaging techniques. Contrast agents that can be used for combined imaging modalities are needed. In this study, the feasibility of using microbubbles containing gadolinium (MCG) as contrast agents for both phase contrast imaging (PCI) and magnetic resonance imaging (MRI) are investigated. MCG were made by encapsulating sulfur hexafluoride (SF6) gas with gadolinium and lyophilized powder. Absorption contrast imaging (ACI) and PCI of MCG were performed and compared in vitro. MCG were injected into the main portal trunk of living rats. PCI and MRI were performed at 2 min and 10 min after MCG injection, respectively. PCI exploited the differences in the refractive index and visibly showed the MCG, which were not detectable by ACI. PCI could facilitate clear revelation of the MCG-infused portal veins. The diameter of the portal veins could be determined by the largest MCG in the same portal vein. The minimum diameter of clearly detected portal veins was about 300 µm by MRI. These results indicate that MCG could enhance both PCI and MRI for imaging portal veins. The detection sensitivity of PCI and MRI could compensate for each other when using MCG contrast agents for animals.

Phase contrast imaging of preclinical portal vein embolization with CO2 microbubbles.

Preoperative portal vein embolization (PVE) is employed clinically to avoid postoperative liver insufficiency. Animal models are usually used to study PVE in terms of mechanisms and pathophysiological changes. PVE is formerly monitored by conventional absorption contrast imaging (ACI) with iodine contrast agent. However, the side effects induced by iodine can give rise to animal damage and death. In this study, the feasibility of using phase contrast imaging (PCI) to show PVE using homemade CO2 microbubbles in living rats has been investigated. CO2 gas was first formed from the reaction between citric acid and sodium bicarbonate. The CO2 gas was then encapsulated by egg white to fabricate CO2 microbubbles. ACI and PCI of CO2 microbubbles were performed and compared in vitro. An additional increase in contrast was detected in PCI. PCI showed that CO2 microbubbles gradually dissolved over time, and the remaining CO2 microbubbles became larger. By PCI, the CO2 microbubbles were found to have certain stability, suggesting their potential use as embolic agents. CO2 microbubbles were injected into the main portal trunk to perform PVE in living rats. PCI exploited the differences in the refractive index and facilitated clear visualization of the PVE after the injection of CO2 microbubbles. Findings from this study suggest that homemade CO2 microbubbles-based PCI is a novel modality for preclinical PVE research.

Molecular evaluation of thrombosis using X-ray phase contrast imaging with microbubbles targeted to P-selectin in mice.

OBJECTIVES: X-ray phase contrast imaging (PCI) provides excellent image contrast by utilizing the phase shift. The introduction of microbubbles into tissues can cause a phase shift to make microbubbles visibly identified on PCI. In this study, we assessed the feasibility of targeted microbubble-based PCI for the detection of thrombosis. METHODS: The absorption and phase contrast images of P-selectin-targeted microbubbles (MBP) were obtained and compared in vitro. MBP, control IgG-targeted microbubbles (MBC), and unbound microbubbles (MBU) were tested for binding specificity on thrombi expressing P-selectin. MBP were used as molecular PCI probes to evaluate P-selectin expression in a mouse model of arteriovenous shunt thrombosis that was created using PE tubes in the bypass outside of the mouse body. RESULTS: PCI clearly showed the microbubbles not viewable via absorption contrast imaging (ACI). In vitro attachment of MBP (91.60 ± 11.63) to thrombi was significantly higher than attachment of MBC (17.80 ± 4.02, P < 0.001) or MBU (9.80 ± 2.59, P < 0.001). In the mouse model of arteriovenous shunt thrombosis, the binding affinity of MBP (15.50 ± 6.25) was significantly greater than that of MBC (0.50 ± 0.84, P < 0.001) or MBU (0.33 ± 0.52, P < 0.001). CONCLUSIONS: Our results indicate that molecular PCI may be considered as a novel and promising imaging modality for the investigation of thrombosis. KEY POINTS: • Small thrombi are rarely detected by conventional radiography. • Phase contrast imaging (PCI) provides higher contrast and spatial resolution than conventional radiography. • P-selectin targeted microbubbles detected by PCI may suggest early thrombosis.

A novel imaging tool for hepatic portal system using phase contrast technique with hydrogen peroxide-generated O2 gas.

The objective of this study was to investigate the potential of hydrogen peroxide-generated oxygen gas-based phase contrast imaging (PCI) for visualizing mouse hepatic portal veins. The O2 gas was made from the reaction between H2O2 and catalase. The gas production was imaged by PCI in real time. The H2O2 was injected into the enteric cavity of the lower sigmoid colon to produce O2 in the submucosal venous plexus. The generated O2 gas could be finally drained into hepatic portal veins. Absorption contrast imaging (ACI) and PCI of O2-filled portal veins were performed and compared. PCI offers high resolution and real-time visualization of the O2 gas production. Compared with O2-based ACI, O2-based PCI significantly enhanced the revealing of the portal vein in vivo. It is concluded that O2-based PCI is a novel and promising imaging modality for future studies of portal venous disorders in mice models.

Grating-based phase-contrast imaging of tumor angiogenesis in lung metastases.

PURPOSE: To assess the feasibility of the grating-based phase-contrast imaging (GPI) technique for studying tumor angiogenesis in nude BALB/c mice, without contrast agents. METHODS: We established lung metastatic models of human gastric cancer by injecting the moderately differentiated SGC-7901 gastric cancer cell line into the tail vein of nude mice. Samples were embedded in a 10% formalin suspension and dried before imaging. Grating-based X-ray phase-contrast images were obtained at the BL13W beamline of the Shanghai Synchrotron Radiation Facility (SSRF) and compared with histological sections. RESULTS: Without contrast agents, grating-based X-ray phase-contrast imaging still differentiated angiogenesis within metastatic tumors with high spatial resolution. Vessels, down to tens of microns, showed gray values that were distinctive from those of the surrounding tumors, which made them easily identifiable. The vessels depicted in the imaging study were similar to those identified on histopathology, both in size and shape. CONCLUSIONS: Our preliminary study demonstrates that grating-based X-ray phase-contrast imaging has the potential to depict angiogenesis in lung metastases.

United iterative reconstruction for spectral computed tomography.

Spectral computed tomography (CT) has attracted considerable attention because of its energy-resolving capability in identifying and discriminating materials. The use of a narrow energy bin can improve energy resolution. However, a narrow energy bin has high noise ratio, which degrades the imaging quality of spectral CT. To address this problem, this study exploits the structure correlations of images in the energy domain and proposed two types of united iterative reconstruction (UIR) algorithms. One type uses the well-reconstructed broad-spectrum image, with all available photons, as a constraint, whereas the other type uses a pseudo narrow-energy image, which is estimated with the use of our proposed structure-coupling (SC) method, as a constraint. The SC method utilizes local structures to connect images that are reconstructed with broad-spectrum and narrow-energy CT datasets. Given a broad-spectrum image, the SC method can accurately estimate its corresponding narrow-energy image. Results show that UIR algorithms significantly outperform conventional iterative reconstruction algorithms for narrow-energy image reconstruction in spectral CT. Among the UIR algorithms, SC-UIR yields the best results.

Neurovascular recovery via co-transplanted neural and vascular progenitors leads to improved functional restoration after ischemic stroke in rats.

The concept of the "neurovascular unit," emphasizing the interactions between neural and vascular components in the brain, raised the notion that neural progenitor cell (NPC) transplantation therapy aimed at neural repair may be insufficient for the treatment of ischemic stroke. Here, we demonstrate that enhanced neurovascular recovery via cotransplantation of NPCs and embryonic stem cell-derived vascular progenitor cells (VPCs) in a rat stroke model is correlated with improved functional recovery after stroke. We found that cotransplantation promoted the survival, migration, differentiation, and maturation of neuronal and vascular cells derived from the cotransplanted progenitors. Furthermore, it triggered an increased generation of VEGF-, BDNF-, and IGF1-expressing neural cells derived from the grafted NPCs. Consistently, compared with transplantation of NPCs alone, cotransplantation more effectively improved the neurobehavioral deficits and attenuated the infarct volume. Thus, cotransplantation of NPCs and VPCs represents a more effective therapeutic strategy for the treatment of stroke than transplantation of NPCs alone.