Fathinul Fikri Ahmad Saad

Imaging of nonthrombotic pulmonary embolism: Biological materials, nonbiological materials, and foreign bodies

Nonthrombotic pulmonary embolism is defined as embolization to the pulmonary circulation caused by a wide range of substances of endogenous and exogenous biological and nonbiological origin and foreign bodies. It is an underestimated cause of acute and chronic embolism. Symptoms cover the entire spectrum from asymptomatic patients to sudden death. In addition to obstruction of the pulmonary vasculature there may be an inflammatory cascade that deteriorates vascular, pulmonary and cardiac function. In most cases the patient history and radiological imaging reveals the true nature of the patients condition. The purpose of this article is to give the reader a survey on pathophysiology, typical clinical and radiological findings in different forms of nonthrombotic pulmonary embolism. The spectrum of forms presented here includes pulmonary embolism with biological materials (amniotic fluid, trophoblast material, endogenous tissue like bone and brain, fat, Echinococcus granulosus, septic emboli and tumor cells); nonbiological materials (cement, gas, iodinated oil, glue, metallic mercury, radiotracer, silicone, talc, cotton, and hyaluronic acid); and foreign bodies (lost intravascular objects, bullets, catheter fragments, intraoperative material, radioactive seeds, and ventriculoperitoneal shunts).

Gadolinium-based layered double hydroxide and graphene oxide nano-carriers for magnetic resonance imaging and drug delivery

Gadolinium (Gd)-based contrasts remain one of the most accepted contrast agents for magnetic resonance imaging, which is among the world most recognized noninvasive techniques employed in clinical diagnosis of patients. At ionic state, Gd is considered toxic but less toxic in chelate form. A variety of nano-carriers, including gadolinium oxide (Gd2O3) nanoparticles have been used by researchers to improve the T1 and T2 contrasts of MR images. Even more recently, a few researchers have tried to incorporate contrast agents simultaneously with therapeutic agents using single nano-carrier for theranostic applications. The benefit of this concept is to deliver the drugs, such as anticancer drugs and at the same time to observe what happens to the cancerous cells. The delivery of both agents occurs concurrently. In addition, the toxicity of the anticancer drugs as well as the contrast agents will be significantly reduced due to the presence of the nano-carriers. The use of graphene oxide (GO) and layered double hydroxides (LDH) as candidates for this purpose is the subject of current research, due to their low toxicity and biocompatibility, which have the capacity to be used in theranostic researches. We review here, some of the key features of LDH and GO for simultaneous drugs and diagnostic agents delivery systems for use in theranostics applications.

Systematic review on the accuracy of positron emission tomography/computed tomography and positron emission tomography/magnetic resonance imaging in the management of ovarian cancer: Is functional information really needed?

Ovarian cancer (OC) often presents at an advanced stage with frequent relapses despite optimal treatment; thus, accurate staging and restaging are required for improving treatment outcomes and prognostication. Conventionally, staging of OC is performed using contrast-enhanced computed tomography (CT). Nevertheless, recent advances in the field of hybrid imaging have made positron emission tomography/CT (PET/CT) and PET/magnetic resonance imaging (PET/MRI) as emerging potential noninvasive imaging tools for improved management of OC. Several studies have championed the role of PET/CT for the detection of recurrence and prognostication of OC. We provide a systematic review and meta-analysis of the latest publications regarding the role of molecular imaging in the management of OC. We retrieved 57 original research articles with one article having overlap in both diagnosis and staging; 10 articles (734 patients) regarding the role of PET/CT in diagnosis of OC; 12 articles (604 patients) regarding staging of OC; 22 studies (1429 patients) for detection of recurrence; and 13 articles for prognostication and assessment of treatment response. We calculated pooled sensitivity and specificity of PET/CT performance in various aspects of imaging of OC. We also discussed the emerging role of PET/MRI in the management of OC. We aim to give the readers and objective overview on the role of molecular imaging in the management of OC.

Gadolinium-Doped Gallic Acid-Zinc/Aluminium-Layered Double Hydroxide/Gold Theranostic Nanoparticles for a Bimodal Magnetic Resonance Imaging and Drug Delivery System

We have developed gadolinium-based theranostic nanoparticles for co-delivery of drug and magnetic resonance imaging (MRI) contrast agent using Zn/Al-layered double hydroxide as the nanocarrier platform, a naturally occurring phenolic compound, gallic acid (GA) as therapeutic agent, and Gd(NO3)3 as diagnostic agent. Gold nanoparticles (AuNPs) were grown on the system to support the contrast for MRI imaging. The nanoparticles were characterized using techniques such as Hi-TEM, XRD, ICP-ES. Kinetic release study of the GA from the nanoparticles showed about 70% of GA was released over a period of 72 h. The in vitro cell viability test for the nanoparticles showed relatively low toxicity to human cell lines (3T3) and improved toxicity on cancerous cell lines (HepG2). A preliminary contrast property test of the nanoparticles, tested on a 3 Tesla MRI machine at various concentrations of GAGZAu and water (as a reference) indicates that the nanoparticles have a promising dual diagnostic and therapeutic features to further develop a better future for clinical remedy for cancer treatment.

Impacts of biological and procedural factors on semiquantification uptake value of liver in fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography imaging

BACKGROUND Increased metabolic activity of fluorodeoxyglucose (FDG) in tissue is not only resulting of pathological uptake, but due to physiological uptake as well. This study aimed to determine the impacts of biological and procedural factors on FDG uptake of liver in whole body positron emission tomography/computed tomography (PET/CT) imaging. METHODS Whole body fluorine-18 ((18)F) FDG PET/CT scans of 51 oncology patients have been reviewed. Maximum standardized uptake value (SUVmax) of lesion-free liver was quantified in each patient. Pearson correlation was performed to determine the association between the factors of age, body mass index (BMI), blood glucose level, FDG dose and incubation period and liver SUVmax. Multivariate regression analysis was established to determine the significant factors that best predicted the liver SUVmax. Then the subjects were dichotomised into four BMI groups. Analysis of variance (ANOVA) was established for mean difference of SUVmax of liver between those BMI groups. RESULTS BMI and incubation period were significantly associated with liver SUVmax. These factors were accounted for 29.6% of the liver SUVmax variance. Statistically significant differences were observed in the mean SUVmax of liver among those BMI groups (P<0.05). CONCLUSIONS BMI and incubation period are significant factors affecting physiological FDG uptake of liver. It would be recommended to employ different cut-off value for physiological liver SUVmax as a reference standard for different BMI of patients in PET/CT interpretation and use a standard protocol for incubation period of patient to reduce variation in physiological FDG uptake of liver in PET/CT study.

A bimodal theranostic nanodelivery system based on [graphene oxide-chlorogenic acid-gadolinium/gold] nanoparticles

We have synthesized a bimodal theranostic nanodelivery system (BIT) that is based on graphene oxide (GO) and composed of a natural chemotherapeutic agent, chlorogenic acid (CA) used as the anticancer agent, while gadolinium (Gd) and gold nanoparticles (AuNPs) were used as contrast agents for magnetic resonance imaging (MRI) modality. The CA and Gd guest agents were simultaneously loaded on the GO nanolayers using chemical interactions, such as hydrogen bonding and π–π non-covalent interactions to form GOGCA nanocomposite. Subsequently, the AuNPs were doped on the surface of the GOGCA by means of electrostatic interactions, which resulted in the BIT. The physico–chemical studies of the BIT affirmed its successful development. The X-ray diffractograms (XRD) collected of the various stages of BIT synthesis showed the successive development of the hybrid system, while 90% of the chlorogenic acid was released in phosphate buffer solution (PBS) at pH 4.8. This was further reaffirmed by the in vitro evaluations, which showed stunted HepG2 cancer cells growth against the above 90% cell growth in the control cells. A reverse case was recorded for the 3T3 normal cells. Further, the acquired T1-weighted image of the BIT doped samples obtained from the MRI indicated contrast enhancement in comparison with the plain Gd and water references. The abovementioned results portray our BIT as a promising future chemotherapeutic for anticancer treatment with diagnostic modalities.

Kidney Modeling Using a Polynomial Function

In the analysis methods for dynamic positron emission tomography (dPET) data, compartment model has been recognized as the gold standard. But, the studies on the development and validation of a model are relatively complex and time-consuming. Hence, fast algorithms become frequently used for analysing dPET data and parametric images. The purpose of this study is to simulate the 18F-Fluorodeoxyglucose (18F-FDG) concentration in the kidneys from different individuals by applying polynomial regression function and quantitatively describe the fitted data with R-squared correlation coefficient. Four subjects had been injected intravenously with 18F-FDG dose of 302.29 ± 18.75 MBq prior to dPET/CT kidney scanning. The time–activity curve (TAC) of abdominal aorta and kidneys were plotted based on the drawn region of interest (ROI) in each frame of image acquisitions. The 18F-FDG concentration was measured by averaging the values of entire voxel within the ROI. Four sets of PET data were entered into the polynomial function of MATLAB R2015a software to implement and analyse the model for fitting the observed data. The best fit was stated by a 15th-degree polynomial function for both sides of the kidneys. The mean R-squared for the right kidney is 0.85 while 0.86 is for the left kidney. Therefore, the model developed can simulate the distribution of 18F-FDG concentration in the kidneys using dPET data.

Graphene Oxide as a Nanocarrier for a Theranostics Delivery System of Protocatechuic Acid and Gadolinium/Gold Nanoparticles

We have synthesized a graphene oxide (GO)-based theranostic nanodelivery system (GOTS) for magnetic resonance imaging (MRI) using naturally occurring protocatechuic acid (PA) as an anticancer agent and gadolinium (III) nitrate hexahydrate (Gd) as the starting material for a contrast agent,. Gold nanoparticles (AuNPs) were subsequently used as second diagnostic agent. The GO nanosheets were first prepared from graphite via the improved Hummer’s protocol. The conjugation of the GO and the PA was done via hydrogen bonding and π–π stacking interactions, followed by surface adsorption of the AuNPs through electrostatic interactions. GAGPA is the name given to the nanocomposite obtained from Gd and PA conjugation. However, after coating with AuNPs, the name was modified to GAGPAu. The physicochemical properties of the GAGPA and GAGPAu nanohybrids were studied using various characterization techniques. The results from the analyses confirmed the formation of the GOTS. The powder X-ray diffraction (PXRD) results showed the diffractive patterns for pure GO nanolayers, which changed after subsequent conjugation of the Gd and PA. The AuNPs patterns were also recorded after surface adsorption. Cytotoxicity and magnetic resonance imaging (MRI) contrast tests were also carried out on the developed GOTS. The GAGPAu was significantly cytotoxic to the human liver hepatocellular carcinoma cell line (HepG2) but nontoxic to the standard fibroblast cell line (3T3). The GAGPAu also appeared to possess higher T1 contrast compared to the pure Gd and water reference. The GOTS has good prospects of serving as future theranostic platform for cancer chemotherapy and diagnosis.

PET/CT analysis of 21 patients with breast cancer: physiological distribution of 18F-choline and diagnostic pitfalls:

Objectives 18F-choline is a useful tracer for detecting tumours with high lipogenesis. Knowledge of its biodistribution pattern is essential to recognise physiological variants. The aim of this study was to describe the physiologic distribution of 18F-choline and pitfalls in patients with breast cancer. Methods Twenty-one consecutive patients with breast cancer (10 premenopausal and 11 postmenopausal women; mean age, 52.82 ± 10.71 years) underwent 18F-choline positron emission tomography (PET)/computed tomography (CT) for staging. Whole-body PET/CT was acquired after 40 minutes of 18F-choline uptake. Acquired PET images were measured semiquantitatively. Results All patients showed pitfalls unrelated to breast cancer. These findings were predominantly caused by physiological glandular uptake in the liver, spleen, pancreas, bowels, axial skeleton (85%-100%), inflammation and benign changes (4.76%), appendicular skeleton (4.76%–19.049%), and site contamination (61.9%). In <1%, a concomitant metastatic neoplasm was found. The breast showed higher physiological uptake in premenopausal compared with postmenopausal woman (18F-choline maximum standardised uptake values [g/dL] of the right breast = 2.04 ± 0.404 vs 1.59 ± 0.97 and left breast = 2.00 ± 0.56 vs 1.93 ± 1.28, respectively). Conclusion 18F-choline uptake was higher in premenopausal women. Physiological 18F-choline uptake was observed in many sites, representing possible pathologies.

Synthesis and characterization of protocatechuic acid-loaded gadolinium-layered double hydroxide and gold nanocomposite for theranostic application

A theranostic nanocomposite was developed using anticancer agent, protocatechuic acid (PA) and magnetic resonance imaging (MRI) contrast agent gadolinium nitrate (Gd) for simultaneous delivery using layered double hydroxide (LDH) as the delivery agent. Gold nanoparticles (AuNPs) were adsorbed on the surface of the LDH, which served as a complementary contrast agent. Based on the concept of supramolecular chemistry (SPC) and multimodal delivery system (MDS), the PA and Gd guests were first intercalated into the LDH host and subsequently AuNPs were surface adsorbed as the third guest. The nanohybrid developed was named MAPGAu. The MAPGAu was exposed to various characterizations at different stages of synthesis, starting with XRD analysis, which was used to confirm the intercalation episode and surface adsorption of the guest molecules. Consequently, FESEM, Hi-TEM, XRD, ICP-OES, CHNS, FTIR and UV–Vis analyses were done on the nanohybrids. The result of XRD analysis indicated successful intercalation of the Gd and PA as well the adsorption of AuNPs. The UV–Vis release study showed 90% of the intercalated drug was released at pH 4.8, which is the pH of the cancer cells. The FESEM and TEM micrographs obtained equally confirmed the formation of MAGPAu nanocomposite, with AuNPs conspicuously deposited on the LDH surface. The cytotoxicity study of the nanohybrid also showed insignificant toxicity to normal cell lines and significant toxicity to cancer cell lines. The developed MAGPAu nanocomposite has shown prospects for future theranostic cancer treatment.