Validation of a Denoising Method Using Deep Learning-Based Reconstruction to Quantify Multiple Sclerosis Lesion Load on Fast FLAIR Imaging.

BACKGROUND AND PURPOSE: Accurate quantification of WM lesion load is essential for the care of patients with multiple sclerosis. We tested whether the combination of accelerated 3D-FLAIR and denoising using deep learning-based reconstruction could provide a relevant strategy while shortening the imaging examination. MATERIALS AND METHODS: Twenty-eight patients with multiple sclerosis were prospectively examined using 4 implementations of 3D-FLAIR with decreasing scan times (4 minutes 54 seconds, 2 minutes 35 seconds, 1 minute 40 seconds, and 1 minute 15 seconds). Each FLAIR sequence was reconstructed without and with denoising using deep learning-based reconstruction, resulting in 8 FLAIR sequences per patient. Image quality was assessed with the Likert scale, apparent SNR, and contrast-to-noise ratio. Manual and automatic lesion segmentations, performed randomly and blindly, were quantitatively evaluated against ground truth using the absolute volume difference, true-positive rate, positive predictive value, Dice similarity coefficient, Hausdorff distance, and F1 score based on the lesion count. The Wilcoxon signed-rank test and 2-way ANOVA were performed. RESULTS: Both image-quality evaluation and the various metrics showed deterioration when the FLAIR scan time was accelerated. However, denoising using deep learning-based reconstruction significantly improved subjective image quality and quantitative performance metrics, particularly for manual segmentation. Overall, denoising using deep learning-based reconstruction helped to recover contours closer to those from the criterion standard and to capture individual lesions otherwise overlooked. The Dice similarity coefficient was equivalent between the 2-minutes-35-seconds-long FLAIR with denoising using deep learning-based reconstruction and the 4-minutes-54-seconds-long reference FLAIR sequence. CONCLUSIONS: Denoising using deep learning-based reconstruction helps to recognize multiple sclerosis lesions buried in the noise of accelerated FLAIR acquisitions, a possibly useful strategy to efficiently shorten the scan time in clinical practice.

Factors affecting renal function in 119 985 adults over three years.

Blood pressure, proteinuria and serum creatinine (SCr) were examined in 119 985 adults, aged 40 years and older, who attended annual health examinations both in 1993 and 3 years later. Renal function was assessed from SCr; changes in individuals' renal function were estimated using the slope of the regression line for the reciprocal of the SCr level vs. time (slope of rSCr) over the 3-year period. Age-dependent SCr concentration increments were observed; however, there was no significant age-dependent change in the slope of rSCr. SCr in hypertensives on anti-hypertensive medication was significantly higher than that in untreated hypertensives, borderline hypertensives and normotensives. The slopes of rSCr in hypertensives (treated, untreated and borderline) were steeper than normotensives in males, and that in untreated hypertensives was steeper than other groups in females. In hypertensives with proteinuria, SCr was higher and renal function deteriorated more rapidly, compared with hypertensives without proteinuria. Hypertension with proteinuria appears to be an important indicator for progressive decline in renal function, this trend being more obvious in males. Renal function decreases with age; however, the rate of decline is constant. The influences of proteinuria and blood pressure on renal function are different in males and females.

Phosphoramidon, an inhibitor of endothelin-converting enzyme, prevents indomethacin-induced gastric mucosal damage in rats.

Endothelin-1 (ET-1) is produced from inactive precursor big ET-1 by endothelin-converting enzyme-1 (ECE-1), a membrane-bound metalloprotease, structurally similar to another metalloprotease, neutral endopeptidase 24.11 (NEP). Although both phosphoramidon and thiorphan are metalloprotease inhibitors, the ECE activity is inhibited by phosphoramidon but not by thiorphan, a specific inhibitor of NEP. Therefore, to investigate whether an ECE inhibitor can prevent indomethacin-induced gastric mucosal damage in rats, we compared the effects between the two metalloprotease inhibitors on both gastric mucosal integrity and the levels of ET-1 and big ET-1 in gastric tissue. Phosphoramidon significantly decreased ET-1 levels, causing a concomitant big ET-1 increase and dose-dependently attenuated indomethacin-induced gastric mucosal damage. By contrast, thiorphan neither changed the ratio of ET-1/big ET-1 nor attenuated the damage. In conclusion, the prevention of gastric mucosal damage by an ECE inhibitor indicates that endogenous ET-1 may play an important role in the pathogenesis of indomethacin-induced gastric mucosal damage.

Cooperative Clinical Trial of Photodynamic Therapy for Early Gastric Cancer With Photofrin Injection and YAG-OPO Laser.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) treats malignant tumors using photosensitizers and light. We employed a new pulse laser as the excitation light source for PDT, i.e. an optical parametric oscillator (OPO) system pumped by a Q-switched Nd:YAG laser, because it provides extremely high peak power. STUDY DESIGN/MATERIALS AND METHODS: The effects of PDT using the photosensitizer Photofrin((R)) and the new laser were evaluated in 12 patients with early gastric cancer. RESULTS: Complete responses (CR) were obtained in 75% of 12 assessable patients, CR was observed in all cases with mucosal carcinoma (response rate 100%).Regarding toxicity, mild photosensitivity was seen in one case and it lasted several weeks. The other major side effect was decrease of total protein, which was observed in six patients (40%), lasting several months. There were no serious abnormalities in symptoms or laboratory tests. CONCLUSION: We conclude that the YAG-OPO laser is suitable as an excitation light source for PDT.

A Clinical Study of Photodynamic Therapy for Superficial Esophageal Carcinoma by YAG-OPO Laser.

A cooperative clinical study of photodynamic therapy (PDT) for superficial esophageal carcinoma was conducted at 6 medical institution. PHE (2mg/kg) with high tumor affinity was used as the oncotropic compound. The light source was a pulse wave YAG-OPO laser with high penetration into the tissue. Irradiation was performed at an energy density of 60-180 J/cm(2) 48-72 h after PHE administration. Eight lesions in 6 patients were treated. All were type 0-II superficial carcinomas. The depth of invasion was EP-MM for 6 lesions and SM for 2 lesions. A complete response (CR) was achieved in all patients after one session of PDT. Five adverse events, including anemia and fever, were reported by 4 patients, but all were WHO grade 2 or lower and transient. PDT using PHE and YAG-OPO laser was therefore considered effective as a curative therapy for superficial esophageal carcinoma.

Gastric mucosal injury induced by local ischemia-reperfusion in rats. Role of endogenous endothelin-1 and free radical.

We investigated the role of an endogenous vasoconstrictor peptide endothelin-1 (ET-1) and free radicals in local gastric ischemia-reperfusion injury in rats. Local gastric ischemia was induced by clamping the left gastric artery for 15 min and reperfusion was done for 10-30 min in the presence of 150 mM exogenous HCl intragastrically. Local gastric ischemia and reperfusion resulted in significant macroscopic and microscopic gastric mucosal damage together with elevation of gastric tissue ET-1 concentration. Gastric tissue ET-1 was found to increase after 15 min of ischemia alone and also with 30 min of reperfusion. A novel nonpeptide endothelin receptor antagonist, bosentan, or a combination of radical scavengers (superoxide dismutase, catalase, and deferoxamine) both attenuated gastric mucosal injury. However, the greater protection observed with bosentan than with radical scavengers might reflect a preferential role of endothelin-1 in this type of injury.

Bosentan, a novel synthetic mixed-type endothelin receptor antagonist, attenuates acute gastric mucosal lesions induced by indomethacin and HCl in the rat: role of endogenous endothelin-1.

Endothelin-1 has been reported to be responsible for gastric mucosal damage in various experimental models. We evaluated the role of endogenous endothelin-1 in the pathogenesis of gastric mucosal damage induced by indomethacin and HCl in the rat. Rats were given indomethacin (25 mg/kg) subcutaneously, and 15 min later, 0.2N HCl intragastrically. Gastric mucosal damage, gastric endogenous endothelin-1, and gastric mucosal hemodynamics were measured. The effects of bosentan, a mixed endothelin receptor antagonist, on gastric mucosal integrity and hemodynamics were assessed. Gastric endogenous endothelin-1 was significantly elevated at 20 min, gastric mucosal blood flow began to decrease significantly at 25 min, and gastric damage occupied 52.2% of the total glandular mucosa at 135 min after injection of indomethacin. Intragastric pretreatment with bosentan (5, 10, 30, and 60 mg/kg) significantly attenuated gastric damage, to 26.1%, 7.7%, 3.6%, and 1.6%, respectively, of the total glandular mucosa. Bosentan (60 mg/kg) prevented the initial decrease of blood flow and, even at 135 min, improved blood flow and hemoglobin oxygen saturation significantly. We suggest that indomethacin-induced endogenous endothelin-1 diminishes gastric mucosal blood flow and tissue oxygenation and ultimately causes gastric damage. Endogenous endothelin-1 may play an important role in the pathogenesis of the acute gastric mucosal lesions induced by indomethacin and HCl.

Transforming growth factor-alpha (TGF alpha)-producing gastric carcinoma with acanthosis nigricans: an endocrine effect of TGF alpha in the pathogenesis of cutaneous paraneoplastic syndrome and epithelial hyperplasia of the esophagus.

A case of well-differentiated adenocarcinoma (Borrmann type 3) of the stomach in a 76-year-old man associated with the typical skin manifestations of acanthosis nigricans and with multiple protruding lesions showing epithelial hyperplasia of the esophagus is reported. The advanced tumor was located in the cardiac region of the stomach, and measured approximately 8 cm in diameter, with partial invasion to the esophagus. The associated cutaneous lesions were characterized by hyperpigmentation and by protruding verrucous papules on the torso, head, face, neck, upper extremities, perineum, and inguinal region. Histologically, the protruding skin lesions showed keratinocytes proliferation throughout the epidermis, resulting in diffuse hyperkeratosis, papillomatosis, and acanthosis of the skin. Immunohistological analysis showed coexpression of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) receptors in the tumor from the stomach. It is reasonable to conclude from this evidence that gastric carcinoma cells secrete TGF alpha in an autocrine for auto-stimulation. EGF receptor expression was also noted on the papillomatous hyperplasia of the cutaneous lesion. Serum level of TGF alpha, determined by an enzyme-linked immunosorbent assay, was high (144 pg/ml; normal, 22.0 +/- 16 pg/ml (Mean +/- SD)). Serum TGF alpha abruptly decreased to 49 pg/ml on day 7 after the total gastrectomy, and then gradually increased to 77 pg/ml within 28 days. Amelioration of the cutaneous lesions and the protruding lesions in the esophagus was observed after surgical resection of the gastric carcinoma. This suggests that the TGF alpha stimulates the proliferation of keratinocytes involved with EGF receptor. Large amounts of circulating TGF alpha in the blood over a long period released by the primary tumor seem to act as an endocrine-like mechanism causing epidermal and esophageal epithelial cells to proliferate. There is a possible link in the pathogenesis of the acanthosis nigricans as a cutaneous paraneoplastic syndrome, and epithelial hyperplasia of the esophagus.

Phosphoramidon, an endothelin converting enzyme inhibitor attenuates local gastric ischemia-reperfusion injury in rats.

Recently increased production of endothelin-1 has been implicated in the pathogenesis of gastric ischemia-reperfusion injury. We have investigated the effects of endothelin converting enzyme inhibition on local gastric ischemia-reperfusion injury in rats by using two metalloprotease inhibitors, phosphoramidon and thiorphan. In presence of exogenous 0.15M HCI intragastrically, local ischemia was induced by the clamping of left gastric artery for 15 min and reperfusion was done for 30 min. In separate group of rats, phosphoramidon (10-60 mg/kg) or thiorphan (60 mg/kg) were given as i.v. bolus injection immediately before the induction of ischemia. Phosphoramidon dose dependently attenuated the macroscopic and microscopic mucosal injuries while thiorphan did not. These results indicate that phosphoramidon-sensitive endothelin converting enzyme activity is highly present in stomach and phosphoramidon, by inhibiting the conversion of big endothelin-1 to endothelin-1 attenuated the gastric mucosal damage in this model.

Natural history of a spontaneous dissecting aneurysm of the proximal superior mesenteric artery: report of a case.

We report herein the case of a 44-year-old man in whom an asymptomatic dissecting aneurysm was found in the proximal part of the superior mesenteric artery (SMA) during a preoperative evaluation for colon cancer. The patient was managed conservatively with blood pressure control during the perioperative period of the colon resection as the false lumen of the dissecting aneurysm was revealed to be completely occluded by thrombus. The thrombus in the false lumen continued to be absorbed until 1 month after surgery. The patient is currently well 4 years after his operation without any evidence of recurrence of the aneurysm.

Role of transforming growth factor-beta in the restitution of injured guinea pig gastric mucosa in vitro.

The role of transforming growth factor-beta (TGF-beta) in restitution was examined in intact sheets of injured guinea pig gastric mucosa in which the epithelial cell-collagen interaction can be quantitatively evaluated. The luminal surface of intact sheets of in vitro guinea pig gastric mucosa was injured by exposure to 1.25 mol/l NaCl for 10 min. Restitution was evaluated by measurement of transmucosal electrical resistance and [3H]mannitol flux before and after injury. Recovery of electrical resistance and [3H]mannitol flux was retarded by inhibition of endogenous TGF-beta with either aprotinin or anti-TGF-beta antibody; effects were restored by human recombinant TGF-beta1. During inhibition of endogenous TGF-beta, type IV collagen accelerated the recovery. Inhibition of reconstruction of the basement membrane by simultaneous addition of cis-4-OH-L-proline and anti-type IV collagen completely abolished the enhancement of the recovery by TGF-beta 1. These results suggest that endogenous TGF-beta is required for restitution to occur in guinea pig gastric mucosa and that type IV collagen plays an important role in TGF-beta-abetted restitution.

Cloning of the Pseudomonas aeruginosa gene encoding CDP-diglyceride synthetase.

The CDP-diglyceride synthetase (CDS)-encoding gene (cds) from Pseudomonas aeruginosa PAO1 was cloned and sequenced. The gene possessed an open reading frame of 813 bp capable of encoding a putative polypeptide of 271 amino acids (aa) (28 699 Da). The deduced aa sequence of CDS revealed a 67% similarity (45% identity) to Escherichia coli CDS.

Primary diaphragmatic schwannoma with a typical target appearance: correlation of CT and MR imagings and histologic findings.

A rare case of benign diaphragmatic schwannoma in a 38-year-old female is reported. Precontrast computed tomography (CT) showed an encapsulated well-defined round homogeneous tumor with central calcification, measuring approximately 5 cm in diameter, arising from the left diaphragm. Contrast-enhanced CT and gadolinium-enhanced T1-weighted magnetic resonance (MR) imaging showed focal enhancement in the central portion of the tumor. The tumor showed a typical target appearance of increased peripheral signal intensity and decreased central signal intensity on unenhanced T2-weighted images. Pathological examination of resected specimens of the tumor showed two zonal histological components: a hypercellular portion of spindle cells with nuclear palisading (Antoni A tissue) and a hypocellular portion of cells with cystic degeneration, together with focal calcification and hemangeomatous vascular changes (Antoni B tissue). We consider the radiological characteristics of diaphragmatic schwannoma on CT and MR imagings to represent the geographic difference between the histologic zones of the tumor.

[Allelic chromosomal deletion using microsatellite polymorphism--the clue to the positional cloning of the tumor suppressor genes responsible for gastric carcinoma].

Cancers are caused by an accumulation of multiple genetic lesions that we are now beginning to understand. Gastric cancer has a different morphological appearance, ability to invade or metastasize, and response to treatment. The pattern of loss of heterozygosity is similar, but not necessarily the same among the different pathological lesions. It is likely that several unknown tumor suppressor genes could be participate in tumor behavior. Positional cloning using microsatellite genes would facilitate the identification of such additional tumor suppressor genes in the genome.

Comparison of [3H]YM060 binding to native and cloned rat 5-HT3 receptors.

We characterized [3H]YM060 ([methyl-3H]-(-)-(R)-5-[(methyl-1H- indol-3-yl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazole monohydrochloride) binding in membrane homogenates prepared from three different rat tissues (cerebral cortex, ileum and colon), and compared the binding characteristics between the native and cloned rat 5-HT3 receptors. The dissociation constant (Kd) of [3H]YM060 was similar in all membranes. In competition studies, the affinity of 5-HT3 receptor agonists and antagonists was similar between the native and the cloned rat 5-HT3 receptors. In conclusion, intra-species difference of 5-HT3 receptor was not observed in rats and pharmacological properties of the cloned rat 5-HT3 receptor were nearly identical to that of the native rat 5-HT3 receptor.

L-arginine and endogenous nitric oxide protect the gastric mucosa from endothelin-1-induced gastric ulcers in rats.

We have reported that endothelin-1 induces gastric ulcer characterized by a potent long-lasting vasoconstriction of the regional microvasculature. Nitric oxide synthesized from L-arginine has been shown to regulated gastric mucosal blood flow, and inhibition of its synthesis has been shown to delay the healing of gastric ulcers. We examined the effect of exogenous L-arginine and the inhibition of nitric oxide synthesis on the development of endothelin-1-induced gastric ulcers. In rats anesthetized with urethane, a continuous intravenous infusion of L- or D-arginine (10 mg.kg-1.min-1) was followed, 15 min later, by a submucosal injection of endothelin-1 (200 pmol/kg) in the anterior wall of the gastric body. In another group, rats were intravenously pretreated with N omega-nitro-L-arginine-methyl ester (1-10 mg/kg), a nitric oxide synthesis inhibitor, and then injected with endothelin-1 (40 pmol/kg). Twenty-four h later, L-arginine, but not D-arginine, had significantly reduced the extent and the severity of the endothelin-1-induced ulcer (mucosal wall damage, 18.11 +/- 4.79% and 88.14 +/- 7.06%, respectively; mean +/- SD, P < 0.001), and the nitric oxide synthesis inhibitor (10 mg/kg) had increased the endothelin-1-induced mucosal damage (ulcer length, 3.8 +/- 1.2 mm and 1.1 +/- 0.2 mm, respectively, P < 0.01). Continuous gastric mucosal blood flow measurements showed that L-arginine antagonized the endothelin-1-induced vasoconstriction. L-arginine protected the gastric mucosa from the ulcerogenic action of endothelin-1 and antagonized its vasoconstrictive action. The inhibition of endogenous nitric oxide potentiated the ulcerogenic effect of endothelin-1 on rat gastric mucosa.

Primary tubular adenocarcinoma arising in the duodenal limb of reconstructed gastroduodenostomy for signet-ring cell carcinoma of the stomach.

Adenocarcinoma of the small intestine is uncommon. Due to this paucity and the lack of specificity of symptoms, patients are usually seen late in the course of their illness, when curative therapy, mainly represented by extensive surgical resection, is unlikely. The authors report a case of primary well-differentiated tubular adenocarcinoma (T4N0M0) arising in the duodenal limb of a reconstructed Billroth I gastroduodenostomy, 9 years after a distal gastrectomy for signet-ring cell carcinoma of the stomach (T4N0M0). Evidence for excluding the possibility of a recurrence of the primary gastric cancer was based on the different histologic pattern, the long disease-free interval, and other features of the second neoplasm. Relatively early diagnosis of the neoplasm, followed by curative surgical therapy was made possible by the early onset of the obstructive symptoms and the favorable anatomical location of the tumor.

Venous tumor thrombosis and cavernous transformation of the portal vein in a patient with gastric carcinoma.

A case of extensive extra- and intrahepatic portal tumor thrombosis, with no metastatic foci in liver parenchyma, secondary to advanced gastric carcinoma in a 69-year-old man is reported. The portal tumor thrombosis was characterized by enlargement of the thrombosed segment of the vein, decreased density mass without intraluminal enhancement of the involved vein, nonvisualization of the portal venous branch in the involved lobe, and the so-called cavernous transformation of the portal vein. The surgically resected gastric specimen showed Borrmann type 3 advanced papillary adenocarcinoma. The portal tumor thrombus is presumed to have arisen from vascular invasion in the primary foci of gastric carcinoma, and then to have permeated the portal vein without invasion of liver parenchyma.