Clinical Imaging Modalities Research Articles

Quantitative micro-elastography: imaging of tissue elasticity using compression optical coherence elastography.

Probing the mechanical properties of tissue on the microscale could aid in the identification of diseased tissues that are inadequately detected using palpation or current clinical imaging modalities, with potential to guide medical procedures such as the excision of breast tumours. Compression optical coherence elastography (OCE) maps tissue strain with microscale spatial resolution and can delineate microstructural features within breast tissues. However, without a measure of the locally applied stress, strain provides only a qualitative indication of mechanical properties. To overcome this limitation, we present quantitative micro-elastography, which combines compression OCE with a compliant stress sensor to image tissue elasticity. The sensor consists of a layer of translucent silicone with well-characterized stress-strain behaviour. The measured strain in the sensor is used to estimate the two-dimensional stress distribution applied to the sample surface. Elasticity is determined by dividing the stress by the strain in the sample. We show that quantification of elasticity can improve the ability of compression OCE to distinguish between tissues, thereby extending the potential for inter-sample comparison and longitudinal studies of tissue elasticity. We validate the technique using tissue-mimicking phantoms and demonstrate the ability to map elasticity of freshly excised malignant and benign human breast tissues.

Three-dimensional reconstruction of a vascular network by dynamic tracking of magnetite nanoparticles.

Visualization of small blood vessels feeding tumor sites provides important information on the tumors and their microenvironment. This information plays an important role in targeted drug therapies using magnetic gradients. However, capabilities of current clinical imaging modalities may be insufficient to resolve complex microvascular networks. The purpose of this study is to map the vascular network, 3D, based on the magnetic susceptibility contrast. Magnetic particles induce an inhomogeneity in the MRI's magnetic field in an order much larger than their real size. This is an approach to compensate the spatial resolution insufficiency of a clinical MR scanner. Micron-sized agglomerations of magnetite nanoparticles were injected in a 3D phantom vascular network, and a fast multislice, multiacquisition MR sequence was applied to track the agglomerations along their trajectories. The experiment was performed twice for two different imaging planes: coronal and transversal. The susceptibility artifact in the images indicated the presence and the position of the agglomerations. The calculated positions through multiple images were assembled to build up the 3D distribution of the vascular network. The calculated points were compared with the centerline of the channels, extracted from the 3D reference image, to determine the absolute measurement error. The mean error was measured to be approximately half of the pixel's size. It was found that the positioning error on the axis perpendicular to the imaging slice was nearly twice as high as on the imaging plane axes due to the slice thickness. In order to compensate for the lack of resolution on the perpendicular axis, the reconstruction was performed using a combination of coronal and transversal data. The combination of the coordinates led to a significant decrease in the mean measurement error at each segment in the vascular network (p < 0.001). A method for 3D reconstruction of a microvascular network based on the susceptibility contrast in MRI and using a clinical scanner and a commercial receiver coil was proposed. The method presents a novel approach for reconstruction of vascular networks using the susceptibility effect. The proposed method may be applied to resolve vascular networks at a micrometric scale.

Comparison of glenoid inclination angle using different clinical imaging modalities

The β-angle, formed by the intersection of a line on the floor of the supraspinatus fossa and glenoid fossa line, has been described as a reliable measurement tool in the clinical setting to analyze glenoid inclination on the anteroposterior (AP) view of the shoulder. The purpose of this study was to compare the accuracy of the β-angle measurement using different imaging modalities with a validated 3-dimensional (3D) software tool. The β-angle was measured on AP radiographs, unformatted 2-dimensional (2D) computed tomography (CT) scan, and reformatted 2D CT scan in the scapular plane for 51 shoulders of 49 patients undergoing primary total shoulder arthroplasty. Comparison to the glenoid inclination angle calculated by the 3D software was performed. The β-angle measured on reformatted CT scan was found to be the most accurate measurement method, with a mean difference of 1° (standard deviation [SD], 0.5°) with respect to 3D measurement. On AP radiographs, the β-angle was not as accurate, with a mean difference of 3° (SD, 0.7°; P < .006). The β-angle on unformatted 2D CT scan was not a reliable method to measure glenoid inclination, with a mean difference of 10° (SD, 0.9°; P < .0001). The β-angle measured with 2D CT scan formatted in the scapular plane was the most accurate method for measuring glenoid inclination. The β-angle on the AP radiograph is less accurate and reliable. Measurement of the β-angle on an unformatted 2D CT scan is not an acceptable method to determine glenoid inclination.

MRI detection of breast cancer micrometastases with a fibronectin-targeting contrast agent.

Metastasis is the primary cause of death in breast cancer patients. Early detection of high-risk breast cancer, including micrometastasis, is critical in tailoring appropriate and effective interventional therapies. Increased fibronectin expression, a hallmark of epithelial-to-mesenchymal transition, is associated with high-risk breast cancer and metastasis. We have previously developed a penta-peptide CREKA (Cys-Arg-Glu-Lys-Ala)-targeted gadolinium-based magnetic resonance imaging (MRI) contrast agent, CREKA-Tris(Gd-DOTA)3 (Gd-DOTA (4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecyl gadolinium), which binds to fibrin–fibronectin complexes that are abundant in the tumour microenvironment of fast-growing breast cancer. Here we assess the capability of CREKA-Tris(Gd-DOTA)3 to detect micrometastasis with MRI in co-registration with high-resolution fluorescence cryo-imaging in female mice bearing metastatic 4T1 breast tumours. We find that CREKA-Tris(Gd-DOTA)3 provides robust contrast enhancement in the metastatic tumours and enables the detection of micrometastases of size <0.5 mm, extending the detection limit of the current clinical imaging modalities. These results demonstrate that molecular MRI with CREKA-Tris(Gd-DOTA)3 may facilitate early detection of high-risk breast cancer and micrometastasis in the clinic.

Échographie des lésions musculaires

Ultrasound (US) combined with clinical imaging modality is the examination of choice in the investigating of muscle damage. This non-invasive, inexpensive and sensitive examination gives him a place of choice for the diagnosis, monitoring and therapeutic management of traumatic pathologies intrinsic or extrinsic muscle. Ultrasound can confirm clinical diagnosis and quantifies the extent of damage. US monitoring also ensures stabilization of injuries and, if appropriate, make hematoma puncture gestures.

Digital tomosynthesis and high resolution computed tomography as clinical tools for vertebral endplate topography measurements: Comparison with microcomputed tomography

Endplate morphology is understood to play an important role in the mechanical behavior of vertebral bone as well as degenerative processes in spinal tissues; however, the utility of clinical imaging modalities in assessment of the vertebral endplate has been limited. The objective of this study was to evaluate the ability of two clinical imaging modalities (digital tomosynthesis, DTS; high resolution computed tomography, HRCT) to assess endplate topography by correlating the measurements to a microcomputed tomography (μCT) standard. DTS, HRCT, and μCT images of 117 cadaveric thoracolumbar vertebrae (T10–L1; 23 male, 19 female; ages 36–100years) were segmented, and inferior and superior endplate surface topographical distribution parameters were calculated. Both DTS and HRCT showed statistically significant correlations with μCT approaching a moderate level of correlation at the superior endplate for all measured parameters (R2Adj=0.19–0.57), including averages, variability, and higher order statistical moments. Correlation of average depths at the inferior endplate was comparable to the superior case for both DTS and HRCT (R2Adj=0.14–0.51), while correlations became weak or nonsignificant for higher moments of the topography distribution. DTS was able to capture variations in the endplate topography to a slightly better extent than HRCT, and taken together with the higher speed and lower radiation cost of DTS than HRCT, DTS appears preferable for endplate measurements.

Histopathological correlations of appendectomies: a clinical audit of a single center.

Acute appendicitis is a common presentation in surgical assessment units and appendectomy accounts for a large number of emergency operations in the UK. Histopathological examination of the appendectomy specimens are routinely carried out. The aim of this study is to correlate the histological findings of appendectomy specimens with the clinical diagnosis of acute appendicitis. This is a retrospective analysis of 238 appendectomies carried out in a single UK center between January and December 2013. The Histopathology reports of appendectomy specimens were retrieved. A total of 238 appendectomies were performed during the study period. The mean age of the patients was 32 years (range, 7-81 years). Adult patients (>16 years) represented 79.4% of the study population. The female sex accounted for 46.6% of all the patients. Of the 238 resected appendix, 211 (88.7%) had histopathology findings consistent with appendicitis. Approximately 1.7% of the 238 specimens were abnormal pathologies other than inflammation of the appendix. The negative appendectomy (normal appendix on histology) rate was 11.3%. The female sex accounted for 59.1% of the negative appendectomies. Adults (>16 years) represented 77.8% of the negative appendectomies. The observed high rates of negative appendectomy in the female sex can be reduced by utilizing combined clinical assessment and diagnostic imaging modalities. The findings of abnormal pathologies on histopathological examination of the appendix which could potentially impact on the management of the patients justify the current practice of routine histopathological examination of resected appendix.

Utility of Gallium-68 DOTANOC PET/CT in the localization of Tumour-induced osteomalacia.

Tumour-induced osteomalacia (TIO) is a rare disorder characterized by hypophosphataemic osteomalacia caused by small mesenchymal tumours secreting fibroblast growth factor 23 (FGF 23). The most difficult part in the management of these patients is the localization of tumours causing TIO. We describe the utility of Gallium (Ga)-68 DOTANOC PET/CT in the localization of tumours causing TIO. The study was conducted in a single tertiary referral university teaching hospital in India. Ten patients with TIO who underwent Ga-68 DOTANOC PET/CT from the time period 2009 to 2014 were included in this study. Their detailed clinical history, biochemical parameters, imaging modalities, surgical interventions, histopathology and outcomes were reviewed. Ga-68 DOTANOC PET/CT could correctly localize the tumours in TIO in 9 of the 10 cases in which it was performed. Complete resection of the tumour led to full clinical recovery in six of the ten patients; two patients who had partial resection and one patient who underwent radiofrequency ablation showed partial remission. One patient in whom Ga-68 DOTANOC PET/CT was positive in vertebral body with a low standardized uptake value (SUV) did not show up the tumour on surgery. We conclude that Ga-68 DOTANOC PET/CT can be used as the first imaging modality in patients diagnosed with TIO. The extremely good outcome following the resection of these small otherwise undiagnosed tumours far outweighs its cost even in resource limited settings.

Polymer film-nanoparticle composites as new multimodality, non-migrating breast biopsy markers.

To develop a breast biopsy marker that resists fast and slow migration and has permanent visibility under commonly used imaging modalities. A polymer-nanoparticle composite film was prepared by embedding superparamagnetic iron oxide nanoparticles and a superelastic Nitinol wire within a flexible polyethylene matrix. MRI, mammography, and ultrasound were used to visualize the marker in agar, ex vivo chicken breast, bovine liver, brisket, and biopsy training phantoms. Fast migration caused by the "accordion effect" was quantified after simulated stereotactic, vacuum-assisted core biopsy/marker placement, and centrifugation was used to simulate accelerated long-term (i.e., slow) migration in ex vivo bovine tissue phantoms. Clear marker visualization under MRI, mammography, and ultrasound was observed. After deployment, the marker partially unfolds to give a geometrically constrained structure preventing fast and slow migration. The marker can be deployed through an 11G introducer without fast migration occurring, and shows substantially less slow migration than conventional markers. The polymer-nanoparticle composite biopsy marker is clearly visible on all clinical imaging modalities and does not show substantial migration, which ensures multimodal assessment of the correct spatial information of the biopsy site, allowing for more accurate diagnosis and treatment planning and improved breast cancer patient care. Polymer-nanoparticle composite biopsy markers are visualized using ultrasound, MRI, and mammography. Embedded iron oxide nanoparticles provide tuneable contrast for MRI visualization. Permanent ultrasound visibility is achieved with a non-biodegradable polymer having a distinct ultrasound signal. Flexible polymer-based biopsy markers undergo shape change upon deployment to minimize migration. Non-migrating multimodal markers will help improve accuracy of pre/post-treatment planning studies.

Novel Strategies for the Diagnosis of Posttraumatic Infections in Orthopaedic Trauma Patients.

Orthopaedic infections that occur after trauma are common. Clinical examination, laboratory markers, imaging modalities, and culture and molecular technologies are used to aid the diagnosis of infection. Culture methods comprise the backbone of diagnostic systems used in hospital laboratory settings; however, several studies have questioned the ability of these techniques to adequately identify infections, particularly in cases where orthopaedic implants were used or when the presence of biofilm bacteria is suspected. Advances in imaging and molecular diagnostics can provide orthopaedic surgeons with an improved means of diagnosing and treating infections.

Photoacoustic imaging of human lymph nodes with endogenous lipid and hemoglobin contrast.

Lymph nodes play a central role in metastatic cancer spread and are a key clinical assessment target. Abnormal node vascularization, morphology, and size may be indicative of disease but can be difficult to visualize with sufficient accuracy using existing clinical imaging modalities. To explore the potential utility of photoacoustic imaging for the assessment of lymph nodes, images of ex vivo samples were obtained at multiple wavelengths using a high-resolution three-dimensional photoacoustic scanner. These images showed that hemoglobin based contrast reveals nodal vasculature and lipid-based contrast reveals the exterior node size, shape, and boundary integrity. These two sources of complementary contrast may allow indirect observation of cancer, suggesting a future role for photoacoustic imaging as a tool for the clinical assessment of lymph nodes.

Nonlinear optical microscopy of early stage (ICRS Grade-I) osteoarthritic human cartilage.

In a synovial joint, the articular cartilage is directly affected during the progression of Osteoarthritis (OA). The characterization of early stage modification in extra-cellular matrix of cartilage is essential for detection as well as understanding the progression of disease. The objective of this study is to demonstrate the potential and capability of nonlinear optical microscopy for the morphological investigation of early stage osteoarthritic cartilage. ICRS Grade-I cartilage sections were obtained from the femoral condyle of the human knee. The surface of articular cartilage was imaged by second harmonic generation and two-photon excited fluorescence microscopy. Novel morphological features like microsplits and wrinkles were observed, which would otherwise not be visible in other clinical imaging modalities (e.g., CT, MRI, ultrasound and arthroscope. The presence of superficial layer with distinct collagen fibrils parallel to the articular surface in 4 specimens out of 14 specimens, indicates that different phases of OA within ICRS Grade-I can be detected by SHG microscopy. All together, the observed novel morphologies in early stage osteoarthritic cartilage indicates that SHG microscopy might be a significant tool for the assessment of cartilage disorder.

Response evaluation after primary systemic therapy of Her2 positive breast cancer – an observational cross-sectional study.

AimTo evaluate (I) trastuzumab-containing primary systemic therapy (PST) in human epidermal growth factor receptor 2 (Her2) overexpressing breast carcinomas; (II) compare the patients who achieved and those who did not achieve pathological complete remission (pCR), and (III) analyze the accuracy of different clinical-imaging modalities in tumor response monitoring.Methods188 patients who received PST between 2008 and 2014 were reviewed and 43 Her2 overexpressing breast cancer patients (28 Luminal B/Her2-positive and 15 Her2-positive) were enrolled. 26 patients received mostly taxane-based PST without trastuzumab (Group 1) and 17 patients received trastuzumab-containing PST (Group 2). We compared the concordance between pCR and complete remission (CR) defined by breast-ultrasound, CR defined by standard 18F-fluoro-deoxy-glucose positron emission tomography and computerized tomography (FDG-PET/CT) criteria (Method 1) and CR defined by a novel, breast cancer specific FDG-PET/CT criteria (Method 2). Sensitivity (sens), specificity (spec), and positive (PPV) and negative predictive values (NPV) were calculated.Results10 patients (38.5%) in Group 1 and 8 (47%) in Group 2 achieved pCR. pCR was significantly more frequent in Her2-positive than in Luminal B/Her2-positive tumors in both Group 1 (P = 0.043) and Group 2 (P = 0.029). PET/CT evaluated by the breast cancer specific criteria (PET/CT Method 2) differentiated pCR from non-pCR more accurately in both groups (Group 1: sens = 77.8%, spec = 100%, PPV = 100%, NPV = 71.4%; Group 2: sens = 87.5%, spec = 62.5%, PPV = 70%, NPV = 83.3%) than standard PET/CT criteria (Method 1) (Group 1: sens = 22.2% spec = 100% PPV = 100% NPV = 41.7%; in Group 2: sens = 37.5%, spec = 87.5%, PPV = 75% NPV = 58.3%) or breast ultrasound (Group 1, sens = 83.3% spec = 25% PPV = 62.5% NPV = 50%; Group 2, sens = 100% spec = 12.5% PPV = 41.6% NPV = 100%).ConclusionThe benefit of targeted treatment with trastuzumab-containing PST in Her2 overexpressing breast cancer was defined in terms of pCR rate. Luminal B/Her2-positive subtype needs further subdivision to identify patients who would benefit from PST. Combined evaluation of tumor response by our novel, breast cancer specific FDG-PET/CT criteria accurately differentiated pCR from non-pCR patients.

Role of cardiovascular magnetic resonance in acute coronary syndrome.

Acute coronary syndrome (ACS) represents a life-threatening manifestation of atherosclerosis, which usually occurs in the setting of sudden plaque erosion or rupture with intracoronary thrombosis and partial to complete cessation of the downstream myocardial perfusion.1 The diagnosis, management, and treatment of the various forms of ACS, which include persistent ST-segment elevation myocardial infarction (MI), non-ST-segment elevation MI, and unstable angina (UA), have rapidly been evolving in recent years with subsequently a significant decrease in early and late mortality.2–4 Nevertheless, large multicenter studies have shown despite early and successful reperfusion and optimized medication, the actual hospital mortality remains approximately 7%, not mentioning the evolution towards ischemic heart failure in a considerable number of surviving patients.5 The current diagnostic tools - i.e., blood biomarkers (e.g. troponin), electrocardiography, and ultrasonography - are key tools in the diagnosis of ACS and fast patient triage, but these markers provide only a partial insight in the complex, evolving processes occurring in the jeopardized myocardium.6 Moreover, patients with ACS encompasses a broad and heterogeneous population and many patients with acute chest pain turn out not to have ACS. The accurate diagnosis and differentiation of ACS from other acute cardiac diseases (e.g. aortic dissection, pulmonary embolism, myocarditis, Takotsubo cardiomyopathy) which is essential for therapeutic decision making and specific therapies (e.g. timely reperfusion) may be challenging or even impossible with the above diagnostic tools. Cardiovascular magnetic resonance (CMR) imaging offers the cardiologist a comprehensive view on ACS at the tissue level (e.g. edema, necrosis, microvascular injury, hemorrhage) and may add important information for the diagnosis and differential diagnosis of ACS. As recent studies have demonstrated CMR-derived parameters yield independent prognostic value in addition to traditional risk factors, CMR may be also important for patient risk stratification. Despite the diagnostic and prognostic utility of CMR in ACS many cardiologists are not yet familiar with this fascinating and clinical helpful imaging modality. The aim of this review is therefore to elucidate the role of CMR in this group of cardiac high-risk patients.

Adenovirus-mediated expression of human sodium-iodide symporter gene permits in vivo tracking of adipose tissue-derived stem cells in a canine myocardial infarction model

IntroductionIn vivo tracking of the transplanted stem cells is important in pre-clinical research of stem cell therapy for myocardial infarction. We examined the feasibility of adenovirus-mediated sodium iodide symporter (NIS) gene to cell tracking imaging of transplanted stem cells in a canine infarcted myocardium by clinical single photon emission computed tomography (SPECT). MethodsBeagle dogs were injected intramyocardially with NIS-expressing adenovirus-transfected canine stem cells (Ad-hNIS-canine ADSCs) a week after myocardial infarction (MI) development. 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) and 99mTc-pertechnetate (99mTcO4−) SPECT imaging were performed for assessment of infarcted myocardium and viable stem cell tracking. Transthoracic echocardiography was performed to monitor any functional cardiac changes. ResultsLeft ventricular ejection fraction (LVEF) was decreased after LAD ligation. There was no significant difference in EF between the groups with the stem cell or saline injection. 125I uptake was higher in Ad-hNIS-canine ADSCs than in non-transfected ADSCs. Cell proliferation and differentiation were not affected by hNIS-carrying adenovirus transfection. 99mTc-MIBI myocardial SPECT imaging showed decreased radiotracer uptake in the infarcted apex and mid-anterolateral regions. Ad-hNIS-canine ADSCs were identified as a region of focally increased 99mTcO4− uptake at the lateral wall and around the apex of the left ventricle, peaked at 2 days and was observed until day 9. ConclusionsCombination of adenovirus-mediated NIS gene transfection and clinical nuclear imaging modalities enables to trace the fate of transplanted stem cells in infarcted myocardium for translational in vivo cell tracking study for prolonged duration.

PET/MRI for the body imager: abdominal and pelvic oncologic applications.

The purpose of this pictorial review is to describe emerging clinical applications of positron emission tomography (PET)/magnetic resonance imaging (MRI), the newest clinical hybrid imaging modality, with a specific focus on abdominal and pelvic malignancies. Important issues regarding the clinical implementation of PET/MRI systems, including workflow considerations and protocol development, are examined. The unique technical challenges of simultaneous PET/MRI acquisition and MRI-based attenuation correction are also briefly discussed. This article is intended to provide the body imager with an overview of the potential diagnostic advantages of PET/MRI, as compared to PET/CT or MRI alone.

Diagnosis of Cushing's disease.

Diagnosis of Cushing's disease frequently remains a challenge. In this review we critically appraise the clinical features, biochemical tests, and imaging modalities used for this purpose. We outline recommendations for approaches to clinical investigation, with a particular focus on developments made within the last two years.

Imaging tumor metabolism using positron emission tomography.

Positron emission tomography (PET) is an extraordinarily sensitive clinical imaging modality for interrogating tumor metabolism. Radiolabeled PET substrates can be traced at subphysiological concentrations, allowing noninvasive imaging of metabolism and intratumoral heterogeneity in systems ranging from advanced cancer models to patients in the clinic. There are a wide range of novel and more established PET radiotracers, which can be used to investigate various aspects of the tumor, including carbohydrate, amino acid, and fatty acid metabolism. In this review, we briefly discuss the more established metabolic tracers and describe recent work on the development of new tracers. Some of the unanswered questions in tumor metabolism are considered alongside new technical developments, such as combined PET/magnetic resonance imaging scanners, which could provide new imaging solutions to some of the outstanding diagnostic challenges facing modern cancer medicine.

On the suitability of Elekta’s Agility 160 MLC for tracked radiation delivery: closed-loop machine performance

For motion adaptive radiotherapy, dynamic multileaf collimator tracking can be employed to reduce treatment margins by steering the beam according to the organ motion.The Elekta Agility 160 MLC has hitherto not been evaluated for its tracking suitability. Both dosimetric performance and latency are key figures and need to be assessed generically, independent of the used motion sensor.In this paper, we propose the use of harmonic functions directly fed to the MLC to determine its latency during continuous motion. Furthermore, a control variable is extracted from a camera system and fed to the MLC. Using this setup, film dosimetry and subsequent γ statistics are performed, evaluating the response when tracking (MRI)-based physiologic motion in a closed-loop.The delay attributed to the MLC itself was shown to be a minor contributor to the overall feedback chain as compared to the impact of imaging components such as MRI sequences. Delay showed a linear phase behaviour of the MLC employed in continuously dynamic applications, which enables a general MLC-characterization. Using the exemplary feedback chain, dosimetry showed a vast increase in pass rate employing γ statistics.In this early stage, the tracking performance of the Agility using the test bench yielded promising results, making the technique eligible for translation to tracking using clinical imaging modalities.

Noninvasive imaging of tumor burden and molecular pathways in mouse models of cancer.

Imaging plays a central role in the diagnosis of cancer and the evaluation of therapeutic efficacy in patients with cancer. Because macroscopic imaging is noninvasive and quantitative, the development of specialized instruments for small animals has spurred increasing utilization in preclinical cancer studies. Some small-animal imaging devices are miniaturized derivatives of clinical imaging modalities, including computed tomography, magnetic resonance imaging, positron-emission tomography, single-photon emission computed tomography, and ultrasonography. Optical imaging, including bioluminescence imaging and fluorescence imaging, has evolved from microscopic cellular imaging technologies. Here, we review how current imaging modalities are enabling high-resolution structural imaging with micrometer-scale spatial resolution, thus allowing for the quantification of tumor burden in genetically engineered and orthotopic models of cancer, where tumors develop within organs not typically accessible to measurements with calipers. Beyond measuring tumor size, imaging is increasingly being used to assess the activity of molecular pathways within tumors and to reveal the pharmacodynamic efficacy of targeted therapies. Each imaging technology has particular strengths and limitations, and we discuss how studies should be carefully designed to match the imaging approach to the primary experimental question.