Time-resolved magnetic resonance angiography as a follow-up method for visceral artery aneurysm treated with coil-embolisation

Purpose: The purpose of this study is to assess the feasibility and usefulness of time-resolved magnetic resonance angiography (TR-MRA) for follow-up of visceral artery aneurysms (VAAs) after embolotherapy. Material and methods: Twenty-one VAAs (11 splenic, six renal, three internal iliac, and one superior pancreaticoduodenal artery aneurysms) in 18 patients (median age, 64 years; range, 36-88 years) previously treated by embolisation with platinum coils, were evaluated. The mean size of the aneurysm was 10.5 cm3 (range, 0.3-132 cm3). Among them, 19 lesions were treated by aneurysmal packing with or without distal-to-proximal embolisation. For the remaining two lesions, distal-to-proximal embolization alone was performed. The mean observation period after embolotherapy was 35 weeks (range, 4-216). All patients underwent TR-MRA following an intravenous bolus injection of gadolinium chelate. Recanalisation was diagnosed when any portion of the aneurysmal sac was enhanced in the arterial phase. Results: On TR-MRA, two lesions were diagnosed as recanalised. They were confirmed by transcatheter arteriography and re-treated by embolotherapy. For the remaining 19 lesions, there were no findings of recanalisation on TR-MRA. Conclusions: TR-MRA appears to be a feasible method for follow-up examination of VAAs treated by embolotherapy

Time-resolved magnetic resonance angiography for assessment of recanalization after coil embolization of visceral artery aneurysms

Background: Follow-up imaging after coil embolization of visceral artery aneurysms is important for detecting recanalization. However, CT examination is susceptible to coil artifacts, which sometimes makes it difficult to assess recanalization. We report 2 cases where recanalization was successfully visualized using time-resolved magnetic resonance angiography after coil embolization of visceral artery aneurysms (one case of right internal iliac artery aneurysm and one case of splenic artery aneurysm). Repeat coil embolization was successfully performed. Case Report: Case 1. An 80-year-old male patient with right internal iliac artery (IIA) aneurysm underwent coil embolization. Aneurysm was located at the bifurcation of the right IIA and therefore, after making a femorofemoral bypass, the distal part of the right IIA, aneurysm and the common iliac artery were embolized with a coil. One year later, the size of the aneurysm seemed to have increased on CT. However, the details were not determined because of metal artifacts. Thus, timeresolved MRA was performed and showed minute vascular flow inside the aneurysm. Angiography was subsequently performed and blood flow inside the aneurysm was visualized similar to the findings in time-resolved MRA. Coil embolization was performed once more and vascular flow inside the aneurysm disappeared. Case 2. A 36-year-old male patient with a splenic artery aneurysm underwent coil packing with preservation of splenic artery patency. Four years later, coil compaction was suspected in a CT scan, but CT could not evaluate recanalization because of severe metal artifacts. Angiography was subsequently performed, showing recanalization of the aneurysm as did the time-resolved MRA. Therefore, coil embolization of the aneurysm and splenic artery was performed again. Conclusions: Follow-up imaging after coil embolization of visceral artery aneurysms is important for detecting recanalization. However, it is sometimes difficult to assess recanalization with CT because of artifacts caused by metal. In our cases, recanalization of aneurysms was clearly shown by timeresolved MRA and re-embolization was successfully performed. In conclusion, time-resolved MRA appears to be useful in assessment of recanalization of visceral artery aneurysms after coil embolization

Recombinant human SIRT1 protects against nutrient deprivation-induced mitochondrial apoptosis through autophagy induction in human intervertebral disc nucleus pulposus cells

INTRODUCTION: Nutrient deprivation is a likely contributor to intervertebral disc (IVD) degeneration. Silent mating type information regulator 2 homolog 1 (SIRT1) protects cells against limited nutrition by modulation of apoptosis and autophagy. However, little evidence exists regarding the extent to which SIRT1 affects IVD cells. Therefore, we conducted an in vitro study using human IVD nucleus pulposus (NP) cells. METHODS: Thirty-two IVD specimens were obtained from patients who underwent surgical intervention and were categorized based on Pfirrmann IVD degeneration grades. Cells were isolated from the NP and cultured in the presence of recombinant human SIRT1 (rhSIRT1) under different serum conditions, including 10 % (v/v) fetal bovine serum (FBS) as normal nutrition (N) and 1 % (v/v) FBS as low nutrition (LN). 3-Methyladenine (3-MA) was used to inhibit autophagy. Autophagic activity was assessed by measuring the absorbance of monodansylcadaverine and immunostaining and Western blotting for light chain 3 and p62/SQSTM1. Apoptosis and pathway analyses were performed by flow cytometry and Western blotting. RESULTS: Cells cultured under LN conditions decreased in number and exhibited enhanced autophagy compared with the N condition. Medium supplementation with rhSIRT1 inhibited this decrease in cell number and induced an additional increase in autophagic activity (P < 0.05), whereas the combined use of rhSIRT1 and 3-MA resulted in drastic decreases in cell number and autophagy (P < 0.05). The incidence of apoptotic cell death increased under the LN condition, which was decreased by rhSIRT1 (P < 0.05) but increased further by a combination of rhSIRT1 and 3-MA (P < 0.05). Under LN conditions, NP cells showed a decrease in antiapoptotic Bcl-2 and an increase in proapoptotic Bax, cleaved caspase 3, and cleaved caspase 9, indicating apoptosis induction via the mitochondrial pathway. These changes were suppressed by rhSIRT1 but elevated further by rhSIRT1 with 3-MA, suggesting an effect of rhSIRT1-induced autophagy on apoptosis inhibition. Furthermore, the observed autophagy and apoptosis were more remarkable in cells from IVDs of Pfirrmann grade IV than in those from IVDs of Pfirrmann grade II. CONCLUSIONS: SIRT1 protects against nutrient deprivation-induced mitochondrial apoptosis through autophagy induction in human IVD NP cells, suggesting that rhSIRT1 may be a potent treatment agent for human degenerative IVD disease

Functional impact of integrin α5β1 on the homeostasis of intervertebral discs: a study of mechanotransduction pathways using a novel dynamic loading organ culture system

Background contextIntervertebral disc (IVD) degeneration, a major cause of low back pain, is considered to be induced by daily mechanical loading. Mechanical stress is widely known to affect cell survival and extracellular matrix metabolism in many cell types. Although the involvement of integrin α5β1 transmembrane mechanoreceptor in IVD degeneration has been reported, the precise function of integrin α5β1 remains obscure.PurposeTo reflect IVD tissue response to mechanical stress using a dynamic loading organ culture system and elucidate the functional impact of integrin α5β1 on the pathomechanism of IVD degeneration.Study designAn ex&nbsp;vivo study using a dynamic loading organ culture system.MethodsNinety-six rat IVD explants were examined. Intervertebral discs were subjected to 1.3 MPa, 1.0 Hz dynamic compressive load in the presence or absence of an Arg-Gly-Asp (RGD) peptide with affinity to the fibronectin binding-site of integrin α5β1. Cell viability and histomorphology were assessed. The localization of integrin α5β1 in the IVD was assessed by immunohistochemistry. Gene expression levels of IVD cells were evaluated using real-time reverse transcription-polymerase chain reaction.ResultsIn the nucleus pulposus (NP), cell density and viability were reduced by dynamic compressive load. Histologic degenerative alterations, mainly seen in the NP, were the morphologic changes of NP cells. In both NP and annulus fibrosus (AF), immunohistochemistry revealed localization of integrin α5β1 and that the messenger-RNA expression of integrin α5β1 was increased by&nbsp;dynamic load. Dynamic load induced a catabolic effect, the stimulation of matrix metalloproteinase-3 and -13 gene expressions by NP and AF cells. The RGD peptide partially blocked the histologic alterations and the catabolic effect.ConclusionsThe dynamic loading organ culture system simulated cellular responses to mechanical loading of the IVD. Our results suggest that IVD cells recognize the mechanical stress through RGD integrins, particularly the α5β1 subtype that is highly expressed in NP and AF cells. Further experiments using this system will provide information about pathomechanisms of IVD degeneration through the mechanotransduction pathways