Publications by authors named "Raja Aamir"

8 Publications

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Spectral CT imaging of human osteoarthritic cartilage via quantitative assessment of glycosaminoglycan content using multiple contrast agents.

APL Bioeng 2021 Jun 1;5(2):026101. Epub 2021 Apr 1.

Department of Radiology, University of Otago Christchurch, Christchurch 8011, New Zealand.

Detection of early osteoarthritis to stabilize or reverse the damage to articular cartilage would improve patient function, reduce disability, and limit the need for joint replacement. In this study, we investigated nondestructive photon-processing spectral computed tomography (CT) for the quantitative measurement of the glycosaminoglycan (GAG) content compared to destructive histological and biochemical assay techniques in normal and osteoarthritic tissues. Cartilage-bone cores from healthy bovine stifles were incubated in 50% ioxaglate (Hexabrix) or 100% gadobenate dimeglumine (MultiHance). A photon-processing spectral CT (MARS) scanner with a CdTe-Medipix3RX detector imaged samples. Calibration phantoms of ioxaglate and gadobenate dimeglumine were used to determine iodine and gadolinium concentrations from photon-processing spectral CT images to correlate with the GAG content measured using a dimethylmethylene blue assay. The zonal distribution of GAG was compared between photon-processing spectral CT images and histological sections. Furthermore, discrimination and quantification of GAG in osteoarthritic human tibial plateau tissue using the same contrast agents were demonstrated. Contrast agent concentrations were inversely related to the GAG content. The GAG concentration increased from 25 g/ml (85 mg/ml iodine or 43 mg/ml gadolinium) in the superficial layer to 75 g/ml (65 mg/ml iodine or 37 mg/ml gadolinium) in the deep layer of healthy bovine cartilage. Deep zone articular cartilage could be distinguished from subchondral bone by utilizing the material decomposition technique. Photon-processing spectral CT images correlated with histological sections in healthy and osteoarthritic tissues. Post-imaging material decomposition was able to quantify the GAG content and distribution throughout healthy and osteoarthritic cartilage using Hexabrix and MultiHance while differentiating the underlying subchondral bone.
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http://dx.doi.org/10.1063/5.0035312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018795PMC
June 2021

Winds of change in imaging of calcium crystal deposition diseases.

Joint Bone Spine 2019 Nov 5;86(6):665-668. Epub 2019 May 5.

Department of radiology, University of Otago, Christchurch 8011, New Zealand; MARS Bioimaging Ltd, Christchurch, New Zealand.

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http://dx.doi.org/10.1016/j.jbspin.2019.04.005DOI Listing
November 2019

Clinical Utility of Multi-Energy Spectral Photon-Counting Computed Tomography in Crystal Arthritis.

Arthritis Rheumatol 2019 07 28;71(7):1158-1162. Epub 2019 May 28.

University of Otago, Christchurch, New Zealand.

Objective: To determine whether novel multi-energy spectral photon-counting computed tomography (SPCCT) imaging can detect and differentiate between monosodium urate (MSU), calcium pyrophosphate (CPP), and hydroxyapatite (HA) crystal deposits ex vivo.

Methods: A finger with a subcutaneous gouty tophus and a calcified knee meniscus excised at the time of surgery were obtained. The finger was imaged using plain x-ray, dual-energy CT (DECT), and multi-energy SPCCT. Plain x-ray and multi-energy SPCCT images of the meniscus were acquired. For validation purposes, samples of the crystals were obtained from the tophus and meniscus, and examined by polarized light microscopy and/or x-ray diffraction. As further validation, synthetic crystal suspensions of MSU, CPP, and HA were scanned using multi-energy SPCCT.

Results: Plain x-ray of the gouty finger revealed bone erosions with overhanging edges. DECT and multi-energy SPCCT both showed MSU crystal deposits; SPCCT was able to show finer detail. Plain x-ray of the calcified meniscus showed chondrocalcinosis consistent with CPP, while SPCCT showed and differentiated CPP and HA.

Conclusion: Multi-energy SPCCT can not only detect, differentiate, and quantify MSU crystal deposits in a gouty finger ex vivo, but also specifically detect, identify, and quantify CPP within an osteoarthritic meniscus, and distinguish them from HA crystal deposits. There is potential for multi-energy SPCCT to become useful in the diagnosis of crystal arthropathies.
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http://dx.doi.org/10.1002/art.40848DOI Listing
July 2019

Spectral Photon-Counting Molecular Imaging for Quantification of Monoclonal Antibody-Conjugated Gold Nanoparticles Targeted to Lymphoma and Breast Cancer: An Study.

Contrast Media Mol Imaging 2018 18;2018:2136840. Epub 2018 Dec 18.

Department of Radiology, University of Otago, Christchurch School of Medicine, 2 Riccarton Avenue, Christchurch 8011, New Zealand.

The purpose of the present study was to demonstrate an proof of principle that spectral photon-counting CT can measure gold-labelled specific antibodies targeted to specific cancer cells. A crossover study was performed with Raji lymphoma cancer cells and HER2-positive SKBR3 breast cancer cells using a MARS spectral CT scanner. Raji cells were incubated with monoclonal antibody-labelled gold, rituximab (specific antibody to Raji cells), and trastuzumab (as a control); HER2-positive SKBR3 breast cancer cells were incubated with monoclonal antibody-labelled gold, trastuzumab (specific antibody to HER2-positive cancer cells), and rituximab (as a control). The calibration vials with multiple concentrations of nonfunctionalised gold nanoparticles were used to calibrate spectral CT. Spectral imaging results showed that the Raji cells-rituximab-gold and HER2-positive cells-trastuzumab-gold had a quantifiable amount of gold, 5.97 mg and 0.78 mg, respectively. In contrast, both cell lines incubated with control antibody-labelled gold nanoparticles had less gold attached (1.22 mg and 0.15 mg, respectively). These results demonstrate the proof of principle that spectral molecular CT imaging can identify and quantify specific monoclonal antibody-labelled gold nanoparticles taken up by Raji cells and HER2-positive SKBR3 breast cancer cells. The present study reports the future potential of spectral molecular imaging in detecting tumour heterogeneity so that treatment can be tuned accordingly, leading to more effective personalised medicine.
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http://dx.doi.org/10.1155/2018/2136840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312585PMC
May 2019

Induced macrophage activation in live excised atherosclerotic plaque.

Immunobiology 2018 Aug - Sep;223(8-9):526-535. Epub 2018 Mar 23.

Free Radical Biochemistry Laboratory, School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch, New Zealand; Department of Radiology, University of Otago Christchurch, PO Box 4345, Christchurch, New Zealand. Electronic address:

Atherosclerotic plaques are complex tissues containing many different cell types. Macrophages contribute to inflammation, formation of the necrotic core, and plaque rupture. We examined whether macrophages in plaque can be activated and compared this to monolayer cells. The volume of calcium in the plaque was compared to the level of macrophage activation measured by total neopterin output. Carotid plaque samples were cut into 3 mm sections and cultured for up to 96 h. Live sections were stimulated with interferon-γ, phytohaemagglutinin or phorbol 12-myristate 13-acetate. Macrophage activation and oxidative stress were monitored by total neopterin (oxidized and non-oxidized 7,8-dihydroneopterin) and neopterin levels every 24 h for up to 4 d. The calcium content of two plaques was investigated by spectral imaging. Direct stimulation of macrophages in plaque sections with interferon-γ caused a sustained increase in neopterin (p = .037) and total neopterin (p = .003). The addition of phorbol 12-myristate 13-acetate to plaque had no significant effect on total neopterin production (p = .073) but increased neopterin (p = .037) whereas phytohaemagglutinin caused a significant increase in both neopterin and total neopterin (p = .0279 and .0168). There was an inverse association (R = 0.91) between the volume of calcium and macrophage activation as measured by total neopterin production in stimulated plaque tissue. Resident macrophages within excised carotid plaque activated either directly or indirectly generate the biomarkers 7,8-dihydroneopterin and neopterin. Macrophage activation rather than the oxidative environment is associated with plaque calcification.
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http://dx.doi.org/10.1016/j.imbio.2018.03.002DOI Listing
April 2019

Beam profile assessment in spectral CT scanners.

J Appl Clin Med Phys 2018 Mar 7;19(2):287-297. Epub 2018 Feb 7.

MARS Bioimaging Ltd, Christchurch, New Zealand.

In this paper, we present a method that uses a combination of experimental and modeled data to assess properties of x-ray beam measured using a small-animal spectral scanner. The spatial properties of the beam profile are characterized by beam profile shape, the angular offset along the rotational axis, and the photon count difference between experimental and modeled data at the central beam axis. Temporal stability of the beam profile is assessed by measuring intra- and interscan count variations. The beam profile assessment method was evaluated on several spectral CT scanners equipped with Medipix3RX-based detectors. On a well-calibrated spectral CT scanner, we measured an integral count error of 0.5%, intrascan count variation of 0.1%, and an interscan count variation of less than 1%. The angular offset of the beam center ranged from 0.8° to 1.6° for the studied spectral CT scanners. We also demonstrate the capability of this method to identify poor performance of the system through analyzing the deviation of the experimental beam profile from the model. This technique can, therefore, aid in monitoring the system performance to obtain a robust spectral CT; providing the reliable quantitative images. Furthermore, the accurate offset parameters of a spectral scanner provided by this method allow us to incorporate a more realistic form of the photon distribution in the polychromatic-based image reconstruction models. Both improvements of the reliability of the system and accuracy of the volume reconstruction result in a better discrimination and quantification of the imaged materials.
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http://dx.doi.org/10.1002/acm2.12260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849855PMC
March 2018

Discrimination Between Calcium Hydroxyapatite and Calcium Oxalate Using Multienergy Spectral Photon-Counting CT.

AJR Am J Roentgenol 2017 Nov 23;209(5):1088-1092. Epub 2017 Aug 23.

2 Department of Radiology, University of Otago, Christchurch, New Zealand.

Objective: We aimed to determine whether multienergy spectral photon-counting CT could distinguish between clinically relevant calcium crystals at clinical x-ray energy ranges. Energy thresholds of 15, 22, 29, and 36 keV and tube voltages of 50, 80, and 110 kVp were selected. Images were analyzed to assess differences in linear attenuation coefficients between various concentrations of calcium hydroxyapatite (54.3, 211.7, 808.5, and 1169.3 mg/cm) and calcium oxalate (2000 mg/cm).

Conclusion: The two lower concentrations of hydroxyapatite were distinguishable from oxalate at all energy thresholds and tube voltages, whereas discrimination at higher concentrations depended primarily on the energy thresholds used. Multienergy spectral photon-counting CT shows promise for distinguishing these calcium crystals.
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http://dx.doi.org/10.2214/AJR.17.18394DOI Listing
November 2017
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