IOP Injection, A Novel Superparamagnetic Iron Oxide Particle MRI Contrast Agent for the Detection of Hepatocellular Carcinoma: A Phase II Clinical Trial.

BACKGROUND: MRI is crucial in diagnosing hepatocellular carcinoma (HCC). Superparamagnetic iron oxide particles (SPIO) are liver-specific contrast agents which enhance lesions in T2 -weighted images. Iron oxide nano-particle m-PEG-silane (IOP) Injection, a newly developed SPIO, showed promising imaging effects and good safety profile in preclinical studies and in phase I clinical trial. PURPOSE: To evaluate the safety and clinical validity of IOP Injection as MRI contrast agent in diagnosing HCC. STUDY TYPE: Prospective. SUBJECTS: A total of 52 subjects (61.6 ± 11.05 years, 45 males/7 females) with suspected HCC. FIELD STRENGTH/SEQUENCE: 1.5 T, T1 -weighted in/opposed phase, T2 *-weighted gradient echo, T2 -weighted fast spin echo, true fast imaging with steady-state free precession. ASSESSMENT: Adverse effects and clinical monitoring were recorded throughout the 5-day study. Two independent readers (M.G.H. with 30 years of experience, S.P.K. with 26 years of experience) made the diagnosis. The diagnostic performance of IOP-enhanced MRI was evaluated with sensitivity and positive predictive value by comparing to the pathology reports from subsequent hepatic resection. The number of lesions with various sizes and degrees of differentiation detected by IOP-enhanced MRI was assessed. The relative change in signal intensities over time was indirectly measured from acquired images. STATISTICAL TESTS: Sensitivity and positive predictive value were used to evaluate the diagnostic performance of IOP-enhanced MRI. Prevalence-adjusted and bias-adjusted 𝜅 coefficient was used to assess the interreader variability. RESULTS: No serious adverse event related to IOP Injection was found. IOP Injection enhanced the lesion-to-liver contrast ratio in T2 *-weighted images by 50.1% ± 4.8%. IOP-enhanced MRI detected HCC with 100% sensitivity by subject and 96% sensitivity by lesion. IOP Injection visualized subtle vascular invasion as filling defect within vessels in true fast imaging with steady-state free precession (TrueFISP) images. DATA CONCLUSION: IOP Injection was safe and efficacious as MRI contrast agent in diagnosing HCC in a limited group of subjects. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 2.

Imaging of nanoscale birefringence using polarization-resolved chromatic confocal microscopy.

We demonstrate a homebuilt confocal microscope with ∼60 nm axial resolution to visualize the optical path length (OPL) of liquid crystals (LCs) inside a 2-domain alignment LC cell. Since the microscope is sensitive to light polarization, it is capable of determining LC orientation by accounting for the OPL variation, ΔOPL. The resolution of birefringence depends on the measured ΔOPL from two cross-polarized channel detections, of which the concept is different from other polarization-resolved optical imaging techniques, but is relatively simple in optical layout and analysis. The different orientations of LCs and the voltage-dependent LC rotation properties in the 2-domain LC cell are monitored and analyzed. Additionally, the complicated LC orientation distribution at the junction of the two domains with different alignments can be clearly observed. It shows great possibilities of examining tissue birefringence related to disease progression and tiny birefringence variation of electro-optical materials under an external field, which are hardly resolved by conventional optical imaging techniques.

Determination of time-dependent accumulation of D-lactate in the streptozotocin-induced diabetic rat kidney by column-switching HPLC with fluorescence detection.

For better understanding the complete metabolism and the physiological role of D-lactate, the concentrations of D-lactate in the serum, liver and kidney of normal and diabetic rats were determined by our established column-switching HPLC method with pre-column fluorescence derivatization. Eight-week-old male Sprague-Dawley rats were administered with streptozotocin (STZ) (80 mg/kg) or citrate buffer intraperitoneally. The tissues were then removed and homogenized after 4, 8, 12 and 16 weeks of drug administration, respectively. The homogenates were centrifuged at 1200 × g for 10 min, then the supernatants were derivatized with a fluorescent reagent, 4-nitro-7-piperazino-2,1,3-benzoxadiazole (NBD-PZ), separated on an ODS column followed by a Chiralpak AD-RH chiral column for enantioseparation. The results showed that the D-lactate content elevated in all the 3 examined tissues under diabetic stages. In addition, D-lactate concentrations in rat kidney were accumulated significantly and time-dependently in diabetic groups after receiving STZ for 4, 8, 12 and 16 weeks (2.99, 13.11, 18.19, 23.23 vs. 0.79 µmol/mg protein as control group). Moreover, the kidney of induced 12-week diabetic rat renal showed some histological changes of progressive diabetic nephropathy. The results suggest that D-lactate may be used as a marker of diabetic nephropathy.

Identification of L-3-hydroxybutyrate as an original ketone body in rat serum by column-switching high-performance liquid chromatography and fluorescence derivatization.

L-3-Hydroxybutyrate (L-3HB), the enantiomer of D-3-hydroxybutyrate (D-3HB), has traditionally been regarded the "unnatural" ketone body in mammals, although there is suspicion that it is a more-favorable energy fuel for mammalian tissues than D-3HB. In this study, we demonstrated that L-3HB is an original substance in rat serum by applying fluorescence derivatization and a column-switching high-performance liquid chromatography system as the analysis technique. Racemic 3HB in rat serum derivatized using 4-nitro-7-piperazino-2,1,3-benzoxadiazole was first separated by an ODS column and was further confirmed by verifying the disappearance of the racemic 3HB peak after pretreating rat serum with D-3-hydroxybutyryl dehydrogenase. A switching valve was used to simultaneously introduce isolated racemic 3HB to the enantiomeric separation by two CHIRALCEL OD-RH columns connected in tandem. An L isomer was found to accompany the D isomer, which were quantified to be 3.98 microM (3.61%) and 106.20 microM (96.39%), respectively. Using the present analytical method, the dubious interpretation of the existence of L-3HB was clarified.