Immunoglobulin G4-related disease (IgG4-RD) is a recently discovered systemic condition, in which various organ manifestations are linked by a similar histological appearance. Our knowledge of this condition is still fragmented, as most studies have examined only a few dozen patients or focused on a particular organ manifestation. This study was conducted to learn the demography and patient characteristics of IgG4-RD using a large cohort. A total of 235 consecutive patients with IgG4-RD, diagnosed in 8 general hospitals in the same medical district, were identified by searching the institutions' radiology database. Inclusion criteria were histology-proven IgG4-RD according to the Pathology Consensus Statement and/or definitive type 1 autoimmune pancreatitis meeting the International Consensus Diagnostic Criteria. Clinical notes and images of selected patients were retrospectively reviewed. All patients were adults (M/F = 4/1). The median age was 67 years (range 35-86). Nine tenths were diagnosed in their 50s to 70s. Among 486 manifestations identified in total, the most common was pancreatitis diagnosed in 142 patients (60%), followed by sialadenitis (34%), tubulointerstitial nephritis (23%), dacryoadenitis (23%), and periaortitis (20%). The majority of patients (95%) had at least 1 of the 5 most common manifestations. Male and female patients differed in their organ manifestations (periaortitis more common in males and sialodacryoadenitis more common in females). Serum IgG4 (normal ≤135 mg/dL) was elevated to >135 mg/dL in 208 patients (88%) and >270 mg/dL in 167 (71%). The IgG4 value was significantly higher in patients with multiorgan involvement than in those with a single manifestation (median 629 mg/dL vs 299 mg/dL, P < 0.01). Of 218 patients, for whom both IgG4 and IgG values were available, the IgG4/IgG ratio was raised to >10% in 194 (89%). Corticosteroids were effective, but the relapse rate was estimated to be 24% in the study period (median 37 months). During the follow-up, 15 malignant diseases were diagnosed in 13 patients (6%). This figure is similar to the incidence (12.9 cancers) expected from the Japanese nationwide study for cancer epidemiology (standardized incidence ratio 1.16). In conclusion, this reliable dataset could improve the characterization of IgG4-RD, particularly its unique demography and the frequency of each organ manifestation.

We analysed the haemodynamics of indocyanine green (ICG) in mouse organs and tumours and evaluated responses to anti-angiogenic agents in an allograft tumour mouse model by photoacoustic imaging. Thirty-six male mice (aged 10–14 weeks; body weight 20–25 g) were used. Real-time photoacoustic imaging of organs and tumours after intravenous injection of ICG was conducted in mice until 10 min after ICG injection. ICG distribution in tumour tissues was assessed by immunohistochemical staining and observation of ICG-derived fluorescence. Vascular permeability changes induced by the vascular endothelial growth factor (VEGF)-blocking agent VEGF-trap on tumour photoacoustic signals were studied. The photoacoustic signals in salivary glands and tumours after intravenous injection of iCG (0.604 ± 0.011 and 0.994 ± 0.175 [mean ± standard deviation], respectively) were significantly increased compared with those in the liver, kidney, and great vessel (0.234 ± 0.043, 0.204 ± 0.058 and 0.127 ± 0.040, respectively; p < 0.010). In tumours, the photoacoustic signal increased within 30 s after ICG injection in a dose-dependent manner (r2 = 0.899) and then decreased gradually. ICG was found to extravasate in tumour tissues. In VEGF-trap-treated mice, the photoacoustic signal in the tumour decreased at the early phase before inhibition of tumour growth was detected (0.297 ± 0.052 vs 1.011 ± 0.170 in the control; p < 0.001). Photoacoustic imaging with ICG administration demonstrated extravasation of ICG in mouse organs and tumours, indicating the potential for early detection of changes in vascular permeability during cancer therapy.

To evaluate the utility of photoacoustic imaging in measuring changes in renal oxygen saturation after ischemia-induced acute kidney injury, and to compare these measurements with histological findings and serum levels of kidney function. Acute kidney injury was induced by clamping the left renal pedicle in C57Bl/6 mice, with a 35-min ischemic period used to induce mild renal injury (14 mice) and a 50-min period for severe injury (13 mice). The oxygen saturation was measured before induction, and at 5 time-points over the first 48 h after induction, starting at 4 h after induction. Oxygen saturation, histological score, kidney volume, and the 24 h creatinine clearance rate and serum blood urea nitrogen were also measured on day 28. Between-group differences were evaluated using a Mann-Whitney U-test and Dunn’s multiple comparisons. The association between oxygen saturation and measured variables was evaluated using Spearman’s correlation. A receiver operator characteristic curve was constructed from oxygen saturation values at 24 h after heminephrectomy to predict chronic renal function. The oxygen saturation was higher in the mild than severe renal injury group at 24 h after induction (73.7% and 66.9%, respectively, P<0.05). Between-group comparison on day 28 revealed a higher kidney volume (P = 0.007), lower tubular injury (P<0.001), lower serum level of blood urea nitrogen level (P = 0.016), and lower 24 h creatinine clearance rate (P = 0.042) in the mild compared with the severe injury group. The oxygen saturation at 24 h correlated with the 24 h creatinine clearance rate (P = 0.036) and serum blood urea nitrogen (P<0.001) on day 28, with an area under the receiver operating curve of 0.825. Oxygen saturation, measured by photoacoustic imaging at 24 h after acute kidney injury can predict the extent of subsequent histological alterations in the kidney early after injury.