Synthesis of broad-specificity activity-based probes for exo-ß-mannosidases.

Exo-ß-mannosidases are a broad class of stereochemically retaining hydrolases that are essential for the breakdown of complex carbohydrate substrates found in all kingdoms of life. Yet the detection of exo-ß-mannosidases in complex biological samples remains challenging, necessitating the development of new methodologies. Cyclophellitol and its analogues selectively label the catalytic nucleophiles of retaining glycoside hydrolases, making them valuable tool compounds. Furthermore, cyclophellitol can be readily redesigned to enable the incorporation of a detection tag, generating activity-based probes (ABPs) that can be used to detect and identify specific glycosidases in complex biological samples. Towards the development of ABPs for exo-ß-mannosidases, we present a concise synthesis of ß-manno-configured cyclophellitol, cyclophellitol aziridine, and N-alkyl cyclophellitol aziridines. We show that these probes covalently label exo-ß-mannosidases from GH families 2, 5, and 164. Structural studies of the resulting complexes support a canonical mechanism-based mode of action in which the active site nucleophile attacks the pseudoanomeric centre to form a stable ester linkage, mimicking the glycosyl enzyme intermediate. Furthermore, we demonstrate activity-based protein profiling using an N-alkyl aziridine derivative by specifically labelling MANBA in mouse kidney tissue. Together, these results show that synthetic manno-configured cyclophellitol analogues hold promise for detecting exo-ß-mannosidases in biological and biomedical research.

Differential microstructural and morphological abnormalities in mild cognitive impairment and Alzheimer's disease: Evidence from cortical and deep gray matter.

One aim of this study is to use non-Gaussian diffusion kurtosis imaging (DKI) for capturing microstructural abnormalities in gray matter of Alzheimer's disease (AD). The other aim is to compare DKI metrics against thickness of cortical gray matter and volume of deep gray matter, respectively. A cohort of 18 patients with AD, 18 patients with amnestic mild cognitive impairment (MCI), and 18 normal controls underwent morphological and DKI MR imaging. Images were investigated using regions-of-interest-based analyses for deep gray matter and vertex-wise analyses for cortical gray matter. In deep gray matter, more regions showed DKI parametric abnormalities than atrophies at the early MCI stage. Mean kurtosis (MK) exhibited the largest number of significant abnormalities among all DKI metrics. At the later AD stage, diffusional abnormalities were observed in fewer regions than atrophies. In cortical gray matter, abnormalities in thickness were mainly in the medial and lateral temporal lobes, which fit the locations of known early pathological changes. Microstructural abnormalities were predominantly in the parietal and even frontal lobes, which fit the locations of known late pathological changes. In conclusion, MK can complement conventional diffusion metrics for detecting microstructural changes, especially in deep gray matter. This study also provides evidence supporting the notion that microstructural changes predate morphological changes. Hum Brain Mapp 38:2495-2508, 2017. © 2017 Wiley Periodicals, Inc.

Comparing diffusion weighted imaging with clinical and blood parameters, and with short tau inversion recovery sequence in detecting spinal and sacroiliac joint inflammation in axial spondyloarthritis.

OBJECTIVES: To investigate the usefulness of diffusion weighted imaging (DWI) by comparing with clinical features, blood parameters and traditional short tau inversion recovery (STIR) sequence in detecting spinal and sacroiliac (SI) joint inflammation in axial spondyloarthritis (axSpA) patients. METHODS: One hundred and ten axSpA patients were recruited. Clinical, radiological and blood parameters were recorded. DWI and STIR MRI were performed simultaneously and results were scored according to the Spondyloarthritis Research Consortium of Canada (SPARCC) for comparison. Apparent diffusion coef cient (ADC) values were also calculated. RESULTS: DWI did not correlate with clinical parameters or blood parameters. It also had lowered sensitivity. When compared with STIR sequence, it correlated well with STIR sequence at the SI joint level (CC 0.76, p<0.001), but weakly at the spinal level (CC 0.23, p=0.02). At the SI joint level, the presence of inflammation on both STIR sequence and DWI was associated with an increase in maximum (B=0.24, p=0.02 in STIR; B=0.37, p<0.001 in DWI) and mean ADC values (B=0.17, p=0.003 in STIR; B=0.15, p=0.01 in DWI). Maximum (B=0.19, p=0.04) and mean spinal ADC values (B=0.18, p=0.01) were also positively associated with DWI detected spinal inflammation. Presence of Modic lesions showed positive correlation with STIR sequence (B=7.12, p=0.01) but not spinal ADC values. CONCLUSIONS: Despite DWI correlates with STIR sequence, it has lower sensitivity. However, ADC values appear to be independent of Modic lesions and may supplement STIR sequence to differentiate degeneration.

Hemisphere, gender and age-related effects on iron deposition in deep gray matter revealed by quantitative susceptibility mapping.

The purpose of this work was to investigate the effects of hemispheric location, gender and age on susceptibility value, as well as the association between susceptibility value and diffusional metrics, in deep gray matter. Iron content was estimated in vivo using quantitative susceptibility mapping. Microstructure was probed using diffusional kurtosis imaging. Regional susceptibility and diffusional metrics were measured for the putamen, caudate nucleus, globus pallidus, thalamus, substantia nigra and red nucleus in 42 healthy adults (age range 25-78 years). Susceptibility value was significantly higher in the left than the right side of the caudate nucleus (P = 0.043) and substantia nigra (P < 0.001). Women exhibited lower susceptibility values than men in the thalamus (P < 0.001) and red nucleus (P = 0.032). Significant age-related increases of susceptibility were observed in the putamen (P < 0.001), red nucleus (P < 0.001), substantia nigra (P = 0.004), caudate nucleus (P < 0.001) and globus pallidus (P = 0.017). The putamen exhibited the highest rate of iron accumulation with aging (slope of linear regression = 0.73 × 10(-3) ppm/year), which was nearly twice those in substantia nigra (slope = 0.40 × 10(-3) ppm/year) and caudate nucleus (slope = 0.39 × 10(-3) ppm/year). Significant positive correlations between the susceptibility value and diffusion measurements were observed for fractional anisotropy (P = 0.045) and mean kurtosis (P = 0.048) in the putamen without controlling for age. Neither correlation was significant after controlling for age. Hemisphere, gender and age-related differences in iron measurements were observed in deep gray matter. Notably, the putamen exhibited the highest rate of increase in susceptibility with aging. Correlations between susceptibility value and microstructural measurements were inconclusive. These findings could provide new clues for unveiling mechanisms underlying iron-related neurodegenerative diseases.

Treatment response monitoring in patients with gastrointestinal stromal tumor using diffusion-weighted imaging: preliminary results in comparison with positron emission tomography/computed tomography.

We compared the parameters derived from diffusion-weighted imaging (DWI) and positron emission tomography/computed tomography (PET/CT) for treatment response evaluation and response prediction in patients with gastrointestinal stromal tumor (GIST). Seven patients with histologically proven metastatic disease were enrolled. DWI and PET/CT data were collected from all patients at diagnosis and from six at follow-up. All 37 lesions were identifiable in DWI with a sensitivity of 100%. To achieve higher accuracy, we used the apparent diffusion coefficient (ADC) of liver and background noise as thresholds for the measurement of the ADCs of lesions. Significant inverse correlations were found between ADC(mean_thr) (ADC(mean) with thresholds) and SUV(mean) (mean standardized uptake value) (R(2)=0.523, p<0.001 at diagnosis, and R(2)=0.916, p<0.001 at follow-up), between ADC(mean_thr) and SUV(max) (maximum SUV) (R(2)=0.529, p<0.001 at diagnosis, and R(2)=0.761, p<0.001 at follow-up), between ΔADC(mean_thr) (percentage change in ADC(mean_thr) ) and ΔSUV(mean) (percentage change in SUV(mean) ) (R(2)=0.384, p<0.001), and between ΔADC(mean_thr) and ΔSUV(max) (percentage change in SUV(max) ) (R(2)=0.500, p<0.001). In lesion-based analysis, pre-treatment ADC(mean_thr) outperformed SUV(mean) and SUV(max) in treatment response prediction, with an area under the receiver operating characteristic curve of 0.706. These results show that DWI can provide a quantitative assessment comparable with PET/CT in GIST lesion characterization, treatment response evaluation and response prediction.

Dynamic contrast-enhanced magnetic resonance imaging for characterising nasopharyngeal carcinoma: comparison of semiquantitative and quantitative parameters and correlation with tumour stage.

OBJECTIVES: To evaluate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for characterising nasopharyngeal carcinoma (NPC). METHODS: Forty-five newly diagnosed NPC patients were recruited. The initial enhancement rate (E R ), contrast transfer rate (k ep ), elimination rate (k el ), maximal enhancement (MaxEn) and initial area under the curve (iAUC) were calculated from semiquantitative analysis. The K (trans) (volume transfer constant), v e (volume fraction) and k ep were calculated from quantitative analysis. Student's t-test was used to evaluate the differences among tumour stages. Pearson's correlation between the two sets of k ep was performed. RESULTS: Comparing tumours of T1/2 stage (n = 18) and T3/4 stage (n = 27), MaxEn (P = 0.030) and iAUC (P = 0.039) were both significantly different; however, the iAUC was the only independent variable with 69.6 % sensitivity and 76.5 % specificity respectively; v e was also significantly different (P = 0.010) with 69.6 % sensitivity and 70.6 % specificity respectively. No significant difference was found among N stages. The two sets of k ep s were highly correlated (r = 0.809, P < 0.001). Forty-three patients had chemoradiation, one palliative chemotherapy and one radiotherapy only. In the four patients with poor outcome, k el, E R, MaxEn and iAUC tended to be higher. CONCLUSIONS: Neovasculature in higher T stage NPC exhibits some parameters of increased permeability and perfusion. Thus, DCE-MRI may be helpful as an adjunctive technique in evaluating NPC. KEY POINTS: • The correct assessment of nasopharyngeal carcinoma (NPC) is important for planning treatment. • Neovasculature in higher T stage NPC exhibits increased permeability and perfusion. • Correlation between quantitative and semi-quantitative analysis validates the robustness of DCE-MRI. • DCE-MRI may be helpful as an adjunctive parameter in evaluating NPC.

Diffusion abnormalities in temporal lobes of children with temporal lobe epilepsy: a preliminary diffusional kurtosis imaging study and comparison with diffusion tensor imaging.

In this preliminary study, we aimed to investigate the abnormalities of water diffusion in children with temporal lobe epilepsy (TLE). Eight children with unilateral TLE (according to electroencephalography, EEG) and eight age- and sex-matched controls were recruited. Diffusion tensor imaging (DTI)/diffusional kurtosis imaging (DKI) acquisitions were performed. Radial diffusivity (λ(⊥)), axial diffusivity (λ(∥)), mean diffusivity (MD) and fractional anisotropy (FA) maps were calculated for both DTI and DKI, and radial kurtosis (K(⊥)), axial kurtosis (K(∥)) and mean kurtosis (MK) maps were calculated for DKI only. Mann-Whitney test showed that, for white matter in the temporal lobe, DKI-derived λ(∥) , MD and K(∥) were significantly different in bilateral temporal lobes and EEG-abnormal and EEG-normal sides of the temporal lobe between patients and controls, whereas DTI showed no abnormalities. For gray matter, DKI detected significantly higher MD and MK in the same three comparisons, whereas DTI detected abnormalities only in the comparison between bilateral temporal lobes and between EEG-normal sides in cases and left-right matched sides in controls. No significant difference was observed between EEG-abnormal and EEG-normal sides in cases. These preliminary results indicate that DKI is more sensitive than DTI for the detection of diffusion abnormalities in the temporal lobes of children with TLE, even when EEG signals are normal. These findings pave the way for the application of DKI for in-depth studies on TLE in children.

US findings of melamine-related renal disorders in Hong Kong children.

BACKGROUND: The melamine-tainted milk incident has caused renal disorders in more than 290,000 children from mainland China since the start of the outbreak in 2008. Since then, more than 27,000 children in Hong Kong have undergone renal US screening. OBJECTIVE: To present and discuss the US features of melamine-related renal abnormalities in Hong Kong children. MATERIALS AND METHODS: Between September 2008 and February 2009, 3,835 children attended the Department of Radiology of Princess Margaret Hospital for renal US examination. CT or plain abdominal radiography was performed in those with inconclusive findings. The US findings of detected melamine-related renal disorders were analysed. RESULTS: Echogenic foci in the kidneys were found in 22 children (0.6%). These were located in the renal pelvicalyceal system (in 12 children) and in the renal medulla (in 10 children). The echogenic foci measured 0.1-0.7 cm, with 6 children showing posterior acoustic shadowing, 14 showing comet-tail artefacts, and 2 showing echogenic dots. CONCLUSION: The incidence of renal disorders amongst Hong Kong children exposed to melamine was lower than in their mainland China counterparts. The renal stones detected were also relatively small, with most demonstrating comet-tail artefacts instead of posterior acoustic shadowing.

Neuronavigated high-frequency repetitive transcranial magnetic stimulation for chronic post-stroke dysphagia: A randomized controlled study.

OBJECTIVE: There are potential benefits of repetitive transcranial magnetic stimulation (rTMS) in improving swallowing functions after stroke; however, few studies have been performed in the chronic stroke population. This study aims to distil the key effects of rTMS on swallowing functions and swallowing-related quality of life. METHODS: Twenty-two participants with chronic post-stroke dysphagia were randomly assigned into active or sham rTMS groups. Seven participants withdrew from the study, thus data from 15 participants (mean age 64.6 years) were analysed. Participants received 3,000 pulses of 5 Hz rTMS (active: n = 11; sham: n = 4) on the tongue area of the motor cortex for 10 days over a period of 2 weeks. All participants were assessed 1 week before, and 2 months, 6 months and 12 months after stimulation. Outcomes were measured by a videofluoroscopic swallowing study, swallowing-related quality-of-life questionnaire and Iowa Oral Performance Instrument. RESULTS: No statistically significant effects were identified for any outcome measures. CONCLUSION: This study indicates that 5 Hz rTMS applied over the tongue area of the motor cortex is not effective for improving swallowing function in individuals with chronic post-stroke dysphagia. Possible explanations for these non-significant results are dis cussed. Future studies should explore the potential of the current protocol in conjunction with conventional dysphagia therapy.

Prevalence of radiographic parameters predisposing to femoroacetabular impingement in young asymptomatic Chinese and white subjects.

BACKGROUND: Osteoarthritis of the hip is five to ten times more common in white people than in Chinese people. Little is known about the true prevalence of femoroacetabular impingement or its role in the development of osteoarthritis in the Chinese population. A cross-sectional study of both white and Chinese asymptomatic individuals was conducted to compare the prevalences of radiographic features posing a risk for femoroacetabular impingement in the two groups. It was hypothesized that that there would be proportional differences in hip anatomy between the white and Asian populations. METHODS: Pelvic computed tomography scans of 201 subjects (ninety-nine white Belgians and 102 Chinese; 105 men and ninety-six women) without hip pain who were eighteen to forty years of age were assessed. The original axial images were reformatted to three-dimensional pelvic models simulating standardized radiographic views. Ten radiographic parameters predisposing to femoroacetabular impingement were measured: alpha angle, anterior offset ratio, and caput-collum-diaphyseal angle on the femoral side and crossover sign, ischial spine projection, acetabular anteversion angle, center-edge angle, acetabular angle of Sharp, Tönnis angle, and anterior acetabular head index on the acetabular side. RESULTS: The white subjects had a less spherical femoral head than the Chinese subjects (average alpha angle, 56° compared with 50°; p<0.001). The Chinese subjects had less lateral acetabular coverage than the white subjects, with average center-edge angles of 35° and 39° (p<0.001) and acetabular angles of Sharp of 38° and 36° (p<0.001), respectively. A shallower acetabular configuration was predominantly present in Chinese women. CONCLUSIONS: Significant differences in hip anatomy were demonstrated between young asymptomatic Chinese and white subjects. However, the absolute size of the observed differences appears to contrast with the reported low prevalence of femoroacetabular impingement in Chinese individuals compared with the high prevalence in white populations.

Aging in deep gray matter and white matter revealed by diffusional kurtosis imaging.

Diffusion tensor imaging has already been extensively used to probe microstructural alterations in white matter tracts, and scarcely, in deep gray matter. However, results in literature regarding age-related degenerative mechanisms in white matter tracts and parametric changes in the putamen are inconsistent. Diffusional kurtosis imaging is a mathematical extension of diffusion tensor imaging, which could more comprehensively mirror microstructure, particularly in isotropic tissues such as gray matter. In this study, we used the diffusional kurtosis imaging method and a white-matter model that provided metrics of explicit neurobiological interpretations in healthy participants (58 in total, aged from 25 to 84 years). Tract-based whole-brain analyses and regions-of-interest (anterior and posterior limbs of the internal capsule, cerebral peduncle, fornix, genu and splenium of corpus callosum, globus pallidus, substantia nigra, red nucleus, putamen, caudate nucleus, and thalamus) analyses were performed to examine parametric differences across regions and correlations with age. In white matter tracts, evidence was found supportive for anterior-posterior gradient and not completely supportive for retrogenesis theory. Age-related degenerations appeared to be broadly driven by axonal loss. Demyelination may also be a major driving mechanism, although confined to the anterior brain. In terms of deep gray matter, higher mean kurtosis and fractional anisotropy in the globus pallidus, substantia nigra, and red nucleus reflected higher microstructural complexity and directionality compared with the putamen, caudate nucleus, and thalamus. In particular, the unique age-related positive correlations for fractional anisotropy, mean kurtosis, and radial kurtosis in the putamen opposite to those in other regions call for further investigation of exact underlying mechanisms. In summary, the results suggested that diffusional kurtosis can provide measurements in a new dimension that were complementary to diffusivity metrics. Kurtosis together with diffusivity can more comprehensively characterize microstructural compositions and age-related changes than diffusivity alone. Combined with proper model, it may also assist in providing neurobiological interpretations of the identified alterations.

SUV as an adjunct in evaluating disease activity in idiopathic pulmonary fibrosis - a pilot study.

OBJECTIVE: We hypothesize that the standardized uptake value (SUV) from PET/computed tomography (CT) can act as an adjunct to forced vital capacity (FVC) in evaluating disease status in idiopathic pulmonary fibrosis (IPF). METHODS: Eight consecutive male patients diagnosed with IPF were prospectively recruited to undergo full pulmonary function tests, high-resolution computed tomography of the thorax and PET/CT. The corrected mean SUV (rSUVmean) and corrected maximum SUV (rSUVmax) against the mediastinal blood pool were correlated with clinical parameters. Examinations were repeated 6 months later in six patients (2/8 patients had died) and changes were evaluated. Correlation was assessed by Spearman's rank correlation, and statistical significance was considered when the P-value was less than 0.05. RESULTS: The rSUVmean in IPF was negatively correlated with FVC (r=-0.6, P=0.024) and diffusing capacity for carbon monoxide (r=-0.7, P=0.010). The decline in FVC was associated with an increment in rSUVmax (r=-0.9, P=0.019), but no similar observation was made with total CT score (r=-0.1, P=0.787). CONCLUSION: Pulmonary metabolism, rSUVmean, contributes to the functional status of IPF patients, and changes in rSUVmax may serve as an adjunct surrogate marker to FVC in evaluating the disease status in IPF patients.

Correlations between microstructural alterations and severity of cognitive deficiency in Alzheimer's disease and mild cognitive impairment: a diffusional kurtosis imaging study.

OBJECT: Diffusional kurtosis imaging (DKI), a natural extension of diffusion tensor imaging (DTI), can characterize non-Gaussian diffusion in the brain. We investigated the capability of DKI parameters for detecting microstructural changes in both gray matter (GM) and white matter (WM) in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) and sought to determine whether these DKI parameters could serve as imaging biomarkers to indicate the severity of cognitive deficiency. MATERIALS AND METHODS: DKI was performed on 18AD patients and 12 MCI patients. Fractional anisotropy, kurtosis and diffusivity parameters in the temporal, parietal, frontal and occipital lobes were compared between the two groups using Mann-Whitney U test. The correlations between regional DKI parameters and mini-mental state examination (MMSE) score were tested using Pearson's correlation. RESULTS: In ADs, significantly increased diffusivity and decreased kurtosis parameters were observed in both the GM and WM of the parietal and occipital lobes as compared to MCIs. Significantly decreased fractional anisotropy was also observed in the WM of these lobes in ADs. With the exception of fractional anisotropy and radial kurtosis, all the five other DKI parameters exhibited significant correlations with MMSE score in both GM and WM. CONCLUSION: Bearing additional information, the DKI model can provide sensitive imaging biomarkers for assessing the severity of cognitive deficiency in reference to MMSE score and potentially improve early detection and progression monitoring of AD based on characterizing microstructures in both the WM and especially the GM.

Increasing the accuracy of volume and ADC delineation for heterogeneous tumor on diffusion-weighted MRI: correlation with PET/CT.

PURPOSE: To improve the accuracy of volume and apparent diffusion coefficient (ADC) measurements in diffusion-weighted magnetic resonance imaging (MRI), we proposed a method based on thresholding both the b0 images and the ADC maps. METHODS AND MATERIALS: In 21 heterogeneous lesions from patients with metastatic gastrointestinal stromal tumors (GIST), gross lesion were manually contoured, and corresponding volumes and ADCs were denoted as gross tumor volume (GTV) and gross ADC (ADC(g)), respectively. Using a k-means clustering algorithm, the probable high-cellularity tumor tissues were selected based on b0 images and ADC maps. ADC and volume of the tissues selected using the proposed method were denoted as thresholded ADC (ADC(thr)) and high-cellularity tumor volume (HCTV), respectively. The metabolic tumor volume (MTV) in positron emission tomography (PET)/computed tomography (CT) was measured using 40% maximum standard uptake value (SUV(max)) as the lower threshold, and corresponding mean SUV (SUV(mean)) was also measured. RESULTS: HCTV had excellent concordance with MTV according to Pearson's correlation (r=0.984, P<.001) and linear regression (slope = 1.085, intercept = -4.731). In contrast, GTV overestimated the volume and differed significantly from MTV (P=.005). ADC(thr) correlated significantly and strongly with SUV(mean) (r=-0.807, P<.001) and SUV(max) (r=-0.843, P<.001); both were stronger than those of ADC(g). CONCLUSIONS: The proposed lesion-adaptive semiautomatic method can help segment high-cellularity tissues that match hypermetabolic tissues in PET/CT and enables more accurate volume and ADC delineation on diffusion-weighted MR images of GIST.

Assessing local patients' knowledge and awareness of radiation dose and risks associated with medical imaging: a questionnaire study.

INTRODUCTION: To assess the awareness of radiation dose and associated risks caused by radiological procedures among local patients. METHODS: All subjects were recruited by randomly sampling the patients receiving radiological examinations. These subjects were stratified on age, sex and education. The questionnaire was in Chinese and consisted of 28 questions mostly in multiple choice/true-or-false format, divided into three sections examining demographic data, radiation knowledge/awareness and expectations. RESULTS: A total of 173 questionnaires were returned (83 females and 84 females; mean age of 53). Of these, 32.6% had attended college, 32.6% had completed matriculation and 24.4% secondary school. Most subjects underwent CT (75), MRI (70) and PET-CT (18). Education significantly affected the radiation knowledge (P = 0.013). 60.7% and 32.7% were not aware of the radiation-free nature of MRI and USG, respectively. Respectively, 45.4% and 43.5% were of the misconception that Barium enema and Barium swallow studies do not involve radiation. Moreover, 77.6% and 87.9% were aware of the radiation-laden nature of CT and plain X-rays, respectively. Furthermore, 34% and 50%, respectively, think that they are not exposed to radiation at home and on a plane. Regarding the fatal cancer risk from CT, 17.8% chose the correct answer and 62% underestimated the risk. 32.2% correctly estimated the equivalent dose of CT in terms of number of conventional X-rays and 43.2% underestimated the dose. Most (98.2%) were told of the indication, and 42.7% were told the associated radiation dose. CONCLUSION: Patient radiation awareness is unsatisfactory. There is need to increase patient radiation awareness, and to provide them with the necessary information.

Imaging biomarker with T1ρ and T2 mappings in osteoarthritis - in vivo human articular cartilage study.

INTRODUCTION: Osteoarthritis (OA) of the knee is a common and disabling disease worldwide. Its prevalence is increasing in view of the aging population. Changes in collagen content, its orientation and GAG content in the articular cartilage with age are the major features in knee osteoarthritis. These changes in collagen and GAG contents show no manifestation in plain radiography and conventional magnetic resonance imaging (MRI). Nevertheless, early diagnosis of the knee osteoarthritis is of paramount importance clinically in view of the evolution of putative interventions in its early stage. The aim of this project is to identify the relationships between the two imaging biomarkers (i.e. T1ρ and T2 mappings) and the GAG concentration in living human symptomatic cartilage. METHODOLOGY: 28 patients with clinical diagnosis of knee osteoarthritis were enrolled. 7 males and 16 females were recruited and their mean age was 68.1 (ranges from 53 to 84). Conventional PD sequence, T1ρ and T2 mappings were performed for each subject within 1 week before total knee arthroplasty. Articular cartilage from the lateral tibial plateau was harvested and the GAG content in cartilage was determined by using dimethylmethylene blue method. T1ρ mean and T2 values were calculated and correlate with GAG concentration statistically. RESULTS: The mean value T1ρ was 40.3±13.5ms, ranging from 15.3 to 69.3ms and the mean value T2 was 31.0±10.5ms, ranging from 16.1 to 46.9ms. The mean value of GAG content was 80.1±33.3mg, ranging from 24.9 to 166.0mg while the mean value of GAG concentration was 267.4±165.9mg/cm(3), ranging from 91.3 to 760.5mg/cm(3). T2 values were inversely correlated with GAG concentration with R(2)=0.375, p=0.001 while T1ρ values were also inversely correlated with GAG concentration with R(2)=0.200, p=0.025. CONCLUSION: This in vivo study confirmed that T1ρ and T2 values correlate with the GAG concentration in living human knee cartilages which corroborate with the previous works. The later (T2 values) is found more reliable in our study and less controversial in literatures. We postulate that T2 values can serve as a non-invasive imaging biomarker in the progress of knee osteoarthritis in terms of both disease diagnosis and treatment response monitoring.

Correlation of measurements from diffusion weighted MR imaging and FDG PET/CT in GIST patients: ADC versus SUV.

PURPOSE: We investigated the correlation relationship between ADCs measured by MRI and SUVs measured by PET/CT of lesions on GIST (gastrointestinal stromal tumor) patients to verify if MR is able to replace or serve as an alternative to PET/CT in GIST staging and treatment monitoring. MATERIALS AND METHODS: Between September 2010 and January 2011, five patients with histologically proven metastatic GIST in Queen Mary Hospital, Hong Kong were enrolled into our study. All patients underwent both MRI and PET/CT scans at prognosis. Pearson's correlations of twenty-nine lesions were conducted between 5 pairs of ADCs and SUVs values. RESULTS: Lesions in the liver, peritoneum or bowel loops were found by PET/CT and no extra-abdominal lesion was identified. All twenty-nine lesions are identifiable by MRI with sensitivity of 100%. Significant inverse correlation were found between ADC(mean) and SUV(mean) (P=0.006), ADC(mean) and SUV(max) (P=0.010), ADC(min) and SUV(max) (P=0.014), ADC(min) and SUV(mean) (P=0.026), rADC(min) and rSUV(max) (P=0.047). CONCLUSION: DWI is comparable to PET/CT in visually detecting the GIST lesions' location. Significant inverse correlations were found between ADCs from DWIBS and SUVs from PET/CT on data of GIST patients. This finding demonstrates that DWI is potentially capable of offering similar information for diagnosis and treatment response evaluating in GIST's patients as PET/CT does. Furthermore, ADC(min), which is determined by single pixel, is not as reliable as ADC(mean), which is weighted average value of the whole lesion volume.

Dynamic PET-CT studies for characterizing nasopharyngeal carcinoma metabolism: comparison of analytical methods.

OBJECTIVES: To investigate the optimal PET protocol and analytical method to characterize the glucose metabolism in nasopharyngeal carcinoma (NPC). METHODS: Newly diagnosed NPC patients were recruited and a dynamic PET-CT scan was performed. The optimized threshold to derive the arterial input function (AIF) was studied. Two-tissue compartmental kinetic modeling using three, four, and five parameters, Patlak graphical analysis, and time sensitivity (S-factor) analysis were performed. The best compartmental model was determined in terms of goodness of fit, and correlated with Ki from Patlak graphical analysis and the S-factor. The methods with R>0.9 and P<0.05 were considered acceptable. The protocols using two static scans with its retention index (RI=(SUV(2)/SUV(1)-1)×100%, where SUV is the standardized uptake value) were also studied and compared with S-factor analysis. RESULTS: The best threshold of 0.6 was determined and used to derive AIF. The kinetic model with five parameters yields the best statistical results, but the model with k4=0 was used as the gold standard. All Ki values and some S-factors from data between various intervals (10-30, 10-45, 15-30, 15-45, 20-30, and 20-45 min) fulfilled the criteria. The RIs calculated from the S-factor were highly correlated to RI derived from simple two-point static scans at 10 and 30 min (R=0.9, P<0.0001). CONCLUSION: The Patlak graphical analyses and even a 20-min-interval S-factor analysis or simple two-point static scans were shown to be sufficient to characterize NPC metabolism, confirming the clinical feasibility of applying a short dynamic with image-derived AIF or simple two-point static PET scans for studying NPC.