Wnt/ß-catenin-YAP axis in the pathogenesis of primary intraosseous carcinoma NOS, deriving from odontogenic keratocyst.

Odontogenic tumors (OGTs), which originate from cells of odontogenic apparatus and their remnants, are rare entities. Primary intraosseous carcinoma NOS (PIOC), is one of the OGTs, but it is even rarer and has a worse prognosis. The precise characteristics of PIOC, especially in immunohistochemical features and its pathogenesis, remain unclear. We characterized a case of PIOC arising from the left mandible, in which histopathological findings showed a transition from the odontogenic keratocyst to the carcinoma. Remarkably, the tumor lesion of this PIOC prominently exhibits malignant attributes, including invasive growth of carcinoma cell infiltration into the bone tissue, an elevated Ki-67 index, and lower signal for CK13 and higher signal for CK17 compared with the non-tumor region, histopathologically and immunohistopathologically. Further immunohistochemical analyses demonstrated increased expression of ADP-ribosylation factor (ARF)-like 4c (ARL4C) (accompanying expression of ß-catenin in the nucleus) and yes-associated protein (YAP) in the tumor lesion. On the other hand, YAP was expressed and the expression of ARL4C was hardly detected in the non-tumor region. In addition, quantitative RT-PCR analysis using RNAs and dot blot analysis using genomic DNA showed the activation of Wnt/ß-catenin signaling and epigenetic alterations, such as an increase of 5mC levels and a decrease of 5hmC levels, in the tumor lesion. A DNA microarray and a gene set enrichment analysis demonstrated that various types of intracellular signaling would be activated and several kinds of cellular functions would be altered in the pathogenesis of PIOC. Experiments with the GSK-3 inhibitor revealed that ß-catenin pathway increased not only mRNA levels of ankyrin repeat domain1 (ANKRD1) but also protein levels of YAP and transcriptional co-activator with PDZ-binding motif (TAZ) in oral squamous cell carcinoma cell lines. These results suggested that further activation of YAP signaling by Wnt/ß-catenin signaling may be associated with the pathogenesis of PIOC deriving from odontogenic keratocyst in which YAP signaling is activated.

Correlation between diffusion-weighted image-derived parameters and dynamic contrast-enhanced magnetic resonance imaging-derived parameters in the orofacial region.

Background: Diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) are widely used in the orofacial region. Furthermore, quantitative analyses have proven useful. However, a few reports have described the correlation between DWI-derived parameters and DCE-MRI-derived parameters, and the results have been controversial. Purpose: To evaluate the correlation among parameters obtained by DWI and DCE-MRI and to compare them between benign and malignant lesions. Material and Methods: Fifty orofacial lesions were analysed. The apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudodiffusion coefficient (D*) and perfusion fraction (f) were estimated by DWI. For DCE-MRI, TK model analysis was performed to estimate physiological parameters, for example, the influx forward volume transfer constant into the extracellular-extravascular space (EES) (Ktrans) and fractional volumes of EES and plasma components (ve and vp). Results: Both ADC and D showed a moderate positive correlation with ve (ρ = 0.640 and 0.645, respectively). Ktrans showed a marginally weak correlation with f (ρ = 0.296), while vp was not correlated with f or D*; therefore, IVIM perfusion-related parameters and TK model perfusion-related parameters were not straightforward. Both D and ve yielded high diagnostic power between benign lesions and malignant tumours with areas under the curve (AUCs) of 0.830 and 0.782, respectively. Conclusion: Both D and ve were reliable parameters that were useful for the differential diagnosis. In addition, the true diffusion coefficient (D) was affected by the fractional volume of EES.

Usefulness of reconstructed images of Gd-enhanced 3D gradient echo sequences with compressed sensing for mandibular cancer diagnosis: comparison with CT images and histopathological findings.

OBJECTIVES: To compare the delineation of mandibular cancer by 3D T1 turbo field echo with compressed SENSE (CS-3D-T1TFE) images and MDCT images, and to compare both sets of images with histopathological findings, as the gold standard, to validate the accuracy and clinical usefulness of CS-3D-T1TFE reconstruction. METHODS: Twenty-four patients with mandibular squamous cell carcinoma (SCC) who underwent MRI including CS-3D-T1TFE and MDCT examinations before surgery were retrospectively included. For both examinations, 0.5-mm-thick coronal plane images and 0.5-mm-thick plane images perpendicular and parallel to the dentition were constructed. Two radiologists rated bone invasion in three categories indexed by cortical bone, cancellous bone, and mandibular canal (MC), and inter-rater agreement was assessed by weighted kappa statistics. In 20 of the 24 patients who underwent surgery, the correlation of bone invasion with the histopathological evaluation by pathologists was assessed using Pearson's correlation coefficient. Soft-tissue invasion was assessed by diagnosing the presence of invasion into the mylohyoid muscle, gingivobuccal fold, and masticator space, and inter-rater agreement was assessed by kappa statistics. RESULTS: The interobserver agreement for bone invasion assessment was almost perfect with CS-3D-T1TFE and substantial with MDCT. The image evaluations by both observers agreed with the pathological evaluations in 15 of the 20 cases, showing high correlation (r > 0.8). CS-3D-T1TFE also showed higher inter-rater agreement than MDCT for all measures of soft-tissue invasion. CONCLUSIONS: CS-3D-T1TFE reconstructed images were clinically useful in accurately depicting the extent of mandibular cancer invasion and potentially solving the problem of lesion overestimation associated with conventional MRI. KEY POINTS: • Reconstructed CS-3D-T1TFE images were useful for the diagnosis of mandibular cancer. • CS-3D-T1TFE images showed higher inter-rater agreement than MDCT and high correlation with pathological findings. • CS-3D-T1TFE images may solve the problem of overestimation of the tumor extent, which has been associated with MRI in the past.

Gamma distribution model of diffusion MRI for evaluating the isocitrate dehydrogenase mutation status of glioblastomas.

OBJECTIVE: To determine whether the γ distribution (GD) model of diffusion MRI is useful in the evaluation of the isocitrate dehydrogenase (IDH) mutation status of glioblastomas. METHODS: 12 patients with IDH-mutant glioblastomas and 54 patients with IDH-wildtype glioblastomas were imaged with diffusion-weighted imaging using 13 b-values from 0 to 1000 s/mm2. The shape parameter (κ) and scale parameter (θ) were obtained with the GD model. Fractions of three different areas under the probability density function curve (f1, f2, f3) were defined as follows: f1, diffusion coefficient (D) < 1.0×10-3 mm2/s; f2, D > 1.0×10-3 and <3.0×10-3 mm2/s; f3, D > 3.0 × 10-3 mm2/s. The GD model-derived parameters measured in gadolinium-enhancing lesions were compared between the IDH-mutant and IDH-wildtype groups. Receiver operating curve analyses were performed to assess the parameters' diagnostic performances. RESULTS: The IDH-mutant group's f1 (0.474 ± 0.143) was significantly larger than the IDH-wildtype group's (0.347 ± 0.122, p = 0.0024). The IDH-mutant group's f2 (0.417 ± 0.131) was significantly smaller than the IDH-wildtype group's (0.504 ± 0.126, p = 0.036). The IDH-mutant group's f3 (0.109 ± 0.060) was significantly smaller than the IDH-wildtype group's (0.149 ± 0.063, p = 0.0466). The f1 showed the best diagnostic performance among the GD model-derived parameters with the area under the curve value of 0.753. CONCLUSION: The GD model could well describe the pathological features of IDH-mutant and IDH-wildtype glioblastomas, and was useful in the differentiation of these tumors. ADVANCES IN KNOWLEDGE: Diffusion MRI based on the γ distribution model could well describe the pathological features of IDH-mutant and IDH-wildtype glioblastomas, and its use enabled the significant differentiation of these tumors. The γ distribution model may contribute to the non-invasive identification of the IDH mutation status based on histological viewpoint.

Gamma distribution model of diffusion MRI for the differentiation of primary central nerve system lymphomas and glioblastomas.

The preoperative imaging-based differentiation of primary central nervous system lymphomas (PCNSLs) and glioblastomas (GBs) is of high importance since the therapeutic strategies differ substantially between these tumors. In this study, we investigate whether the gamma distribution (GD) model is useful in this differentiation of PNCSLs and GBs. Twenty-seven patients with PCNSLs and 57 patients with GBs were imaged with diffusion-weighted imaging using 13 b-values ranging from 0 to 1000 sec/mm2. The shape parameter (κ) and scale parameter (θ) were obtained with the GD model. Fractions of three different areas under the probability density function curve (f1, f2, f3) were defined as follows: f1, diffusion coefficient (D) <1.0×10-3 mm2/sec; f2, D >1.0×10-3 and <3.0×10-3 mm2/sec; f3, D >3.0 × 10-3 mm2/sec. The GD model-derived parameters were compared between PCNSLs and GBs. Receiver operating characteristic (ROC) curve analyses were performed to assess diagnostic performance. The correlations with intravoxel incoherent motion (IVIM)-derived parameters were evaluated. The PCNSL group's κ (2.26 ± 1.00) was significantly smaller than the GB group's (3.62 ± 2.01, p = 0.0004). The PCNSL group's f1 (0.542 ± 0.107) was significantly larger than the GB group's (0.348 ± 0.132, p<0.0001). The PCNSL group's f2 (0.372 ± 0.098) was significantly smaller than the GB group's (0.508 ± 0.127, p<0.0001). The PCNSL group's f3 (0.086 ± 0.043) was significantly smaller than the GB group's (0.144 ± 0.062, p<0.0001). The combination of κ, f1, and f3 showed excellent diagnostic performance (area under the curve, 0.909). The f1 had an almost perfect inverse correlation with D. The f2 and f3 had very strong positive correlations with D and f, respectively. The GD model is useful for the differentiation of GBs and PCNSLs.

Improved scan method for dental imaging using multidetector computed tomography: a phantom study.

OBJECTIVES: This study aimed to propose an improved scan method to shorten irradiation time and reduce radiation exposure. METHODS: The maxilla of a human head CT phantom and a Catphan phantom were used for qualitative and quantitative assessment, respectively. The phantoms were scanned by a 160-row multidetector CT scanner using volumetric and helical scanning. In volumetric scanning, the tube current varied from 120 to 60 to 30 to 20 mA with a tube voltage of 120 kV. Images were reconstructed with a bone kernel using iterative reconstruction (IR) and filtered back projection. As a reference protocol, helical scanning was performed using our clinical setting with 120 kV. Two dental radiologists independently graded the quality of dental images using a 4-point scale (4, superior to reference; 1, unacceptable). For the quantitative assessment, we assessed the system performance from each scan. RESULTS: There was no significant difference between the image quality of volumetric scanning using the 60 mA protocol reconstructed with IR and that of the reference (3.08 and 3.00, p = 0.3388). The system performance values at 1.0 cycles/mm of volumetric scanning and 60 mA protocol reconstructed with IR and reference were 0.0038 and 0.0041, respectively. The effective dose of volumetric scanning using the 60 mA protocol was 51.8 µSv, which is a 64.2% reduction to that of the reference. CONCLUSIONS: We proposed an improved scan method resulting in a 64.2% reduction of radiation dose with one-fourth of irradiation time by combining volumetric scanning and IR technique in multidetector CT.

Comparison of image quality of head and neck lesions between 3D gradient echo sequences with compressed sensing and the multi-slice spin echo sequence.

BACKGROUND: Although magnetic resonance imaging (MRI) provides excellent soft-tissue contrast, long acquisition times are major disadvantages. PURPOSE: To evaluate the usefulness of compressed sensing (CS) for contrast-enhanced oral and maxillofacial MRI by comparing the 3D T1 turbo field echo with compressed SENSE (CS-3D-T1TFE) sequence with the multi-slice spin echo (MS-SE) sequence as the reference standard. MATERIAL AND METHODS: Thirty patients with orofacial lesions participated in this study. The scan times for MS-SE and CS-3D-T1TFE were 5 min 56 s and 1 min 43 s, respectively. The signal-to-noise ratio (SNR) was calculated for quantitative analysis and seven parameters (degree of lesion conspicuity, motion artifacts, metal artifacts, pulsation artifacts, quality of fat suppression, homogeneity of blood vessel signal intensity, and overall image quality) were evaluated using a 5-point scale (5 = excellent, 1 = unacceptable) by two observers for qualitative analysis. For comparisons between MS-SE and CS-3D-T1TFE, the paired t-test was used. RESULTS: The SNR of CS-3D-T1TFE was higher than or equal to that of MS-SE. The CS-3D-T1TFE scores for motion artifacts, pulsation artifacts, and homogeneity of blood vessel signal intensity were higher than the corresponding MS-SE scores in assessments by both observers. The MS-SE scores for fat suppression were higher than or equal to the CS-3D-T1TFE scores. There were no significant differences in lesion conspicuity, metal artifacts, and overall image quality between the two sequences. CONCLUSION: CS-3D-T1TFE imaging, less than 30% of the scan time for MS-SE, showed no image degradation while retaining equal or higher SNR and image quality.

Arterial Spin Labeling Imaging for the Parotid Glands of Patients with Sjögren's Syndrome.

Sjögren's syndrome (SS) is characterized by hypofunction of the salivary and lacrimal glands. The salivary function is largely dependent upon the blood supply in the glands. However, the diseased states of the gland perfusion are not well understood. The arterial spin labeling (ASL) technique allows noninvasive quantitative assessment of tissue perfusion without the need for contrast agent. Here, we prospectively compared the perfusion properties of the parotid glands between patients with SS and those with healthy glands using ASL MR imaging. We analyzed salivary blood flow (SBF) kinetics of 22 healthy parotid glands from 11 volunteers and 28 parotid glands from 14 SS patients using 3T pseudo-continuous ASL imaging. SBF was determined in resting state (base SBF) and at 3 sequential segments after gustatory stimulation. SBF kinetic profiles were characterized by base SBF level, increment ratio at the SBF peak, and the differences in segments where the peak appeared (SBF types). Base SBFs of the SS glands were significantly higher than those of healthy glands (59.2 ± 22.8 vs. 46.3 ± 9.0 mL/min/100 g, p = 0.01). SBF kinetic profiles of the SS glands also exhibited significantly later SBF peaks (p < 0.001) and higher SBF increment ratios (74 ± 49% vs. 47 ± 39%, p = 0.04) than the healthy glands. The best SBF criterion (= 51.2 mL/min/100 mg) differentiated between control subjects and SS patients with 71% sensitivity and 82% specificity. Taken together, these results showed that the SS parotid glands were mostly hyperemic and the SS gland responses to gustatory stimulation were stronger and more prolonged than those of the healthy glands. The ASL may be a promising technique for assessing the diseased salivary gland vascularization of SS patients.

Effect of clenching on T2 and diffusion parameters of the masseter muscle.

BACKGROUND: Persistent muscle contractions during clenching are considered to be one reason for temporomandibular disorders. However, no report has evaluated the effect of clenching on the masticatory muscles, as measured by magnetic resonance imaging (MRI). PURPOSE: To investigate whether clenching has an effect on either T(2) or the coefficients for diffusion of the masseter muscles (MM), and to evaluate the effect of the distribution of bite force on such indices. MATERIAL AND METHODS: Twenty-three subjects were examined. Bite force was measured by a pressure-sensitive sheet, and the force of the right and the left sides was calculated. MRI was used to evaluate T(2), the apparent diffusion coefficient (ADC), and the primary (lambda(1)), secondary (lambda(2)), and tertiary eigenvalues (lambda(3)). These indices on the stronger side of the bite force were compared to those on the weaker side. Thereafter, the indices were compared between at rest and during clenching. RESULTS: There was no significant difference in any of the indices (T(2), ADC, lambda(1), lambda(2), and lambda(3)) between the side of stronger bite force and the side with weaker. T(2) increased by clenching, and the difference was significant in the side with stronger bite force (P = 0.006). ADC, lambda(1), lambda(2), and lambda(3) increased significantly by clenching (P <0.01, P <0.01, P <0.01, and P <0.01, respectively) on both sides. The percentage of change of lambda(2) by clenching was 26.2+/-15.7% on the stronger side and 26.9+/-18.6% on the weaker side, which was significantly greater than either that of lambda(1) or lambda(3). CONCLUSION: The coefficients for diffusion of the MM were sensitive to change by clenching, and lambda(2) was the most sensitive. Moreover, the relative distribution of the bite forces had no effect on any of the indices.

The development of a novel automated taste stimulus delivery system for fMRI studies on the human cortical segregation of taste.

fMRI indicated that the primary taste cortex is activated not only by taste but also by non-taste information from oral stimuli. Head movements caused by swallowing are very critical problem in fMRI and inherent difficulties to modulate taste stimuli in the mouth exist to elucidate functional segregation of human brain. We developed a novel automated taste stimulus delivery system for fMRI studies to segregate the pure taste area in the primary taste cortex in humans. As a novel intra-oral device, an elliptic cylinder was attached to an individual mouthpiece and then subject placed the tongue tip in it. Using a computer-controlled extra-oral device, the solutions ran through the intra-oral device in constant conditions. Three adult volunteers participated in the experimental session, alternately consisting of 30 pairs of taste stimuli (0.5 mol/l sucrose solution) and control (water) blocks. The typical findings of the three subjects revealed activation only in the primary taste cortex (P<0.001), and none in the secondary taste cortex. This is the first system that delivers the taste stimuli automatically to a standardized area on the subject's tongue under constant conditions, thus allowing us to successfully segregate the pure taste area in the primary taste cortex in humans.