Diagnostics, Volume 8, Issue 1 (March 2018) – 21 articles

The diagnosis of thoracic outlet syndrome (TOS) has long been a controversial and challenging one. Despite common presentations with pain in the neck and upper extremity, there are a host of presenting patterns that can vary within and between the subdivisions of neurogenic, venous, and arterial TOS. Furthermore, there is a plethora of differential diagnoses, from peripheral compressive neuropathies, to intrinsic shoulder pathologies, to pathologies at the cervical spine. Depending on the subdivision of TOS suspected, diagnostic investigations are currently of varying importance, necessitating high dependence on good history taking and clinical examination. Investigations may add weight to a diagnosis suspected on clinical grounds and suggest an optimal management strategy, but in this changing field new developments may alter the role that diagnostic investigations play. In this article, we set out to summarise the diagnostic approach in cases of suspected TOS, including the importance of history taking, clinical examination, and the role of investigations at present, and highlight the developments in this field with respect to all subtypes. In the future, we hope that novel diagnostics may be able to stratify patients according to the exact compressive mechanism and thereby suggest more specific treatments and interventions. Full article

Breast cancer is the second leading cause of cancer death in women. Estimates indicate a nearly 40% breast cancer mortality reduction when screening women annually starting at age 40. Although mammography is well known to be a powerful screening tool in the detection of early breast cancer, it is imperfect, particularly for women with dense breasts. In women with dense breast tissue, the sensitivity of mammography is reduced. Additionally, women with dense breasts have an increased risk of developing breast cancer while mammography has a lower sensitivity. Screening ultrasound, both handheld and automated, is effective in detecting mammographically occult cancer in women with dense tissue. Studies have shown that ultrasound significantly increases detection of clinically important, small, largely invasive, node-negative cancers. The purpose of this review article is to summarize the literature to date regarding screening breast ultrasound, emphasizing differences in cancer detection in high risk and intermediate risk women, and to discuss practical ways to implement screening ultrasound in clinical practice, including automated whole breast ultrasound, as a viable solution to the increasing need for additional screening. Full article

The pupillary light reflex (PLR) describes the constriction and subsequent dilation of the pupil in response to light as a result of the antagonistic actions of the iris sphincter and dilator muscles. Since these muscles are innervated by the parasympathetic and sympathetic nervous systems, respectively, different parameters of the PLR can be used as indicators for either sympathetic or parasympathetic modulation. Thus, the PLR provides an important metric of autonomic nervous system function that has been exploited for a wide range of clinical applications. Measurement of the PLR using dynamic pupillometry is now an established quantitative, non-invasive tool in assessment of traumatic head injuries. This review examines the more recent application of dynamic pupillometry as a diagnostic tool for a wide range of clinical conditions, varying from neurodegenerative disease to exposure to toxic chemicals, as well as its potential in the non-invasive diagnosis of infectious disease. Full article

Here, we present the case of a 64-year-old male patient diagnosed with castration-resistant prostate cancer (CRPC) with bone metastasis, treated with abiraterone prednisone/prednisolone in combination with ²²³Ra-dichloride therapy, who had remission and a subsequent relapse of bone metastasis on repeated bone scans after therapy. We also discuss the possibility of continuing the ²²³Ra-dichloride therapy over the six planned administrations by administering other cycles at the same dose or at higher doses, if shown to be devoid of a significant increase in side effects, based on dosimetry considerations. Full article

Newly diagnosed breast abscesses are generally treated as a medical emergency that may necessitate immediate interventional treatment. At our institution, there is no in-house after-hours coverage for breast ultrasonography. We could find no peer-reviewed studies on the cost-effectiveness or clinical management impact of on-call ultrasound technologist coverage for imaging of breast abscesses. The purposes of this study were to determine the incidence of breast abscess in patients with clinical findings highly suggestive of abscess, identify clinical factors associated with breast abscess in such patients, and determine the impact of after-hours emergent or urgent breast ultrasonography on the clinical management of breast abscesses in both outpatients and inpatients. We retrospectively reviewed 100 after-hours breast ultrasound studies performed at our tertiary care center from 2011 to 2015 for evaluation of a suspected breast abscess. Only 26% of our patients with clinically suspected abscess ultimately had a confirmed abscess. Factors associated with breast abscess were a palpable abnormality and a history of breast surgery within the eight weeks before presentation. After-hours diagnosis of an abscess was associated with after-hours clinical intervention. Of the 74 patients in whom after-hours ultrasound imaging showed no evidence of abscess, only three patients underwent after-hours drainage. Our findings support overnight and weekend breast ultrasound coverage in large tertiary care centers. Full article

Over 90% of prostate cancers over-express prostate specific membrane antigen (PSMA) and these tumor cells may be accurately targeted for diagnosis by ⁶⁸Ga-PSMA-positron emission tomography/computed tomography (⁶⁸Ga-PSMA-PET/CT) imaging. This novel molecular imaging modality appears clinically to have superseded CT, and appears superior to MR imaging, for the detection of metastatic disease. ⁶⁸Ga-PSMA PET/CT has the ability to reliably stage prostate cancer at presentation and can help inform an optimal treatment approach. Novel diagnostic applications of ⁶⁸Ga-PSMA PET/CT include guiding biopsy to improve sampling accuracy, and guiding surgery and radiotherapy. In addition to facilitating the management of metastatic castrate resistant prostate cancer (mCRPC), ⁶⁸Ga-PSMA can select patients who may benefit from targeted systemic radionuclide therapy. ⁶⁸Ga-PSMA is the diagnostic positron-emitting theranostic pair with the beta emitter Lutetium-177 PSMA (¹⁷⁷Lu-PSMA) and alpha-emitter Actinium-225 PSMA (²²⁵Ac-PSMA) which can both be used to treat PSMA-avid metastases of prostate cancer in the molecular tumor-targeted approach of theranostic nuclear oncology. Full article

Isolated congenital vomer agenesis is a very rare and poorly understood condition. In the context of dental work-up by cone-beam computed tomography (CBCT), the explored volume of the facial bones occasionally reveals incidental abnormalities. We report the case of a 13-year old Caucasian female who underwent CBCT for the pre-treatment evaluation of primary failure of tooth eruption affecting the permanent right upper and inferior molars. CBCT depicted a large defect of the postero-inferior part of the nasal septum without associated soft tissue abnormality and without cranio-facial malformation or cleft palate. In the absence of a history of trauma, chronic inflammatory sinonasal disease, neoplasia and drug abuse, a posterior nasal septum defect warrants the diagnosis of vomer agenesis. A discussion of this condition and of salient CBCT features is provided. Full article

Alzheimer’s Disease (AD) and mild cognitive impairment (MCI) are associated with widespread changes in brain structure and function, as indicated by magnetic resonance imaging (MRI) morphometry and 18-fluorodeoxyglucose position emission tomography (FDG PET) metabolism. Nevertheless, the ability to differentiate between AD, MCI and normal aging groups can be difficult. Thus, the goal of this study was to identify the combination of cerebrospinal fluid (CSF) biomarkers, MRI morphometry, FDG PET metabolism and neuropsychological test scores to that best differentiate between a sample of normal aging subjects and those with MCI and AD from the Alzheimer’s Disease Neuroimaging Initiative. The secondary goal was to determine the neuroimaging variables from MRI, FDG PET and CSF biomarkers that can predict future cognitive decline within each group. To achieve these aims, a series of multivariate stepwise logistic and linear regression models were generated. Combining all neuroimaging modalities and cognitive test scores significantly improved the index of discrimination, especially at the earliest stages of the disease, whereas MRI gray matter morphometry variables best predicted future cognitive decline compared to other neuroimaging variables. Overall these findings demonstrate that a multimodal approach using MRI morphometry, FDG PET metabolism, neuropsychological test scores and CSF biomarkers may provide significantly better discrimination than any modality alone. Full article

Recently, a multiplex ELISA (Quansys Biosciences) was developed that measures ferritin, soluble transferrin receptor (sTfR), retinol-binding protein (RBP), C-reactive protein (CRP), α¹-acid glycoprotein (AGP), thyroglobulin, and histidine-rich protein 2. Our primary aim was to conduct a method-comparison study to compare five biomarkers (ferritin, sTfR, RBP, CRP, and AGP) measured with the Quansys assay and a widely-used s-ELISA (VitMin Lab, Willstaett, Germany) with use of serum samples from 180 women and children from Burkina Faso, Cambodia, and Malaysia. Bias and concordance were used to describe the agreement in values measured by the two methods. We observed poor overall agreement between the methods, both with regard to biomarker concentrations and deficiency prevalence estimates. Several measurements were outside of the limit of detection with use of the Quansys ELISA (total n = 42 for ferritin, n = 2 for sTfR, n = 0 for AGP, n = 5 for CRP, n = 22 for RBP), limiting our ability to interpret assay findings. Although the Quansys ELISA has great potential to simplify laboratory analysis of key nutritional and inflammation biomarkers, there are some weaknesses in the procedures. Overall, we found poor comparability of results between methods. Besides addressing procedural issues, additional validation of the Quansys against a gold standard method is warranted for future research. Full article

The review describes the technologies used in the field of breath analysis to diagnose and monitor diabetes mellitus. Currently the diagnosis and monitoring of blood glucose and ketone bodies that are used in clinical studies involve the use of blood tests. This method entails pricking fingers for a drop of blood and placing a drop on a sensitive area of a strip which is pre-inserted into an electronic reading instrument. Furthermore, it is painful, invasive and expensive, and can be unsafe if proper handling is not undertaken. Human breath analysis offers a non-invasive and rapid method for detecting various volatile organic compounds thatare indicators for different diseases. In patients with diabetes mellitus, the body produces excess amounts of ketones such as acetoacetate, beta-hydroxybutyrate and acetone. Acetone is exhaled during respiration. The production of acetone is a result of the body metabolising fats instead of glucose to produce energy. There are various techniques that are used to analyse exhaled breath including Gas Chromatography Mass Spectrometry (GC–MS), Proton Transfer Reaction Mass Spectrometry (PTR–MS), Selected Ion Flow Tube-Mass Spectrometry (SIFT–MS), laser photoacoustic spectrometry and so on. All these techniques are not portable, therefore this review places emphasis on how nanotechnology, through semiconductor sensing nanomaterials, has the potential to help individuals living with diabetes mellitus monitor their disease with cheap and portable devices. Full article

Thoracic outlet syndrome (TOS) is a neurovascular condition involving the upper extremity, which is known to occur in individuals who perform chronic repetitive upper extremity activities. We prospectively evaluate the incidence of TOS in high-performance musicians who played bowed string musicians. Sixty-four high-performance string instrument musicians from orchestras and professional musical bands were included in the study. Fifty-two healthy volunteers formed an age-matched control group. Bilateral upper extremity duplex scanning for subclavian vessel compression was performed in all subjects. Provocative maneuvers including Elevated Arm Stress Test (EAST) and Upper Limb Tension Test (ULTT) were performed. Abnormal ultrasound finding is defined by greater than 50% subclavian vessel compression with arm abduction, diminished venous waveforms, or arterial photoplethysmography (PPG) tracing with arm abduction. Bowed string instruments performed by musicians in our study included violin (41%), viola (33%), and cello (27%). Positive EAST or ULTT test in the musician group and control group were 44%, and 3%, respectively (p = 0.03). Abnormal ultrasound scan with vascular compression was detected in 69% of musicians, in contrast to 15% of control subjects (p = 0.03). TOS is a common phenomenon among high-performance bowed string instrumentalists. Musicians who perform bowed string instruments should be aware of this condition and its associated musculoskeletal symptoms. Full article

Controversies in the treatment of venous thoracic outlet syndrome (VTOS) have been discussed for decades, but still persist. Calls for more objective reporting standards have pushed practice towards comprehensive venous evaluations and interventions after first rib resection (FRR) for all patients. In our practice, we have relied on patient-centered, patient-reported outcomes to guide adjunctive treatment and measure success. Thus, we sought to investigate the use of thrombolysis versus anticoagulation alone, timing of FRR following thrombolysis, post-FRR venous intervention, and FRR for McCleery syndrome (MCS) and their impact on patient symptoms and return to function. All patients undergoing FRR for VTOS at our institution from 4 April 2000 through 31 December 2013 were reviewed. Demographics, symptoms, diagnostic and treatment details, and outcomes were collected. Per “Reporting Standards of the Society for Vascular Surgery for Thoracic Outlet Syndrome”, symptoms were described as swelling/discoloration/heaviness, collaterals, concomitant neurogenic symptoms, and functional impairment. Patient-reported response to treatment was defined as complete (no residual symptoms and return to function), partial (any residual symptoms present but no functional impairment), temporary (initial improvement but subsequent recurrence of any symptoms or functional impairment), or none (persistent symptoms or functional impairment). Sixty FRR were performed on 59 patients. 54.2% were female with a mean age of 34.3 years. Swelling/discoloration/heaviness was present in all but one patient, deep vein thrombosis in 80%, and visible collaterals in 41.7%. Four patients had pulmonary embolus while 65% had concomitant neurogenic symptoms. In addition, 74.6% of patients were anticoagulated and 44.1% also underwent thrombolysis prior to FRR. Complete or partial response occurred in 93.4%. Of the four patients with temporary or no response, further diagnostics revealed residual venous disease in two and occult alternative diagnoses in two. Use of thrombolysis was not related to FRR outcomes (p = 0.600). Performance of FRR less than or greater than six weeks after the initiation of anticoagulation or treatment with thrombolysis was not related to FRR outcomes (p = 1). Whether patients had DVT or MCS was not related to FRR outcomes (p = 1). No patient had recurrent DVT. From a patient-centered, patient-reported standpoint, VTOS is equally effectively treated with FRR regardless of preoperative thrombolysis or timing of surgery after thrombolysis. A conservative approach to venous interrogation and intervention after FRR is safe and effective for symptom control and return to function. Additionally, patients with MCS are effectively treated with FRR. Full article

Bone scintigraphy is key in imaging skeletal metastases in newly diagnosed prostate cancer. Unfortunately, a notable proportion of scans are not readily classified as positive or negative but deemed indeterminate. The extent of reporting of indeterminate bone scans and how such scans are handled in clinical trials are not known. A systematic review was conducted using electronic databases up to October 2016. The main outcome of interest was the reporting of indeterminate bone scans, analyses of how such scans were managed, and exploratory analyses of the association of study characteristics and the reporting of indeterminate bone scan results. Seventy-four eligible clinical trials were identified. The trials were mostly retrospective (85%), observational (95%), large trials (median 195 patients) from five continents published over four decades. The majority of studies had university affiliation (72%), and an author with imaging background (685). Forty-five studies (61%) reported an indeterminate option for the bone scan and 23 studies reported the proportion of indeterminate scans (median 11.4%). Most trials (44/45, 98%) reported how to handle indeterminate scans. Most trials (n = 39) used add-on supplementary imaging, follow-up bone scans, or both. Exploratory analyses showed a significant association of reporting of indeterminate results and number of patients in the study (p = 0.024) but failed to reach statistical significance with other variables tested. Indeterminate bone scan for staging of prostate cancer was insufficiently reported in clinical trials. In the case of indeterminate scans, most studies provided adequate measures to obtain the final status of the patients. Full article

Recent advances in mobile technology have created a shift towards using battery-driven devices in remote monitoring settings and smart homes. Clinicians are carrying out diagnostic and screening procedures based on the electrocardiogram (ECG) signals collected remotely for outpatients who need continuous monitoring. High-speed transmission and analysis of large recorded ECG signals are essential, especially with the increased use of battery-powered devices. Exploring low-power alternative compression methodologies that have high efficiency and that enable ECG signal collection, transmission, and analysis in a smart home or remote location is required. Compression algorithms based on adaptive linear predictors and decimation by a factor $B/K$ are evaluated based on compression ratio (CR), percentage root-mean-square difference (PRD), and heartbeat detection accuracy of the reconstructed ECG signal. With two databases (153 subjects), the new algorithm demonstrates the highest compression performance ( $\mathrm{CR}=6$ and $\mathrm{PRD}=1.88$ ) and overall detection accuracy (99.90% sensitivity, 99.56% positive predictivity) over both databases. The proposed algorithm presents an advantage for the real-time transmission of ECG signals using a faster and more efficient method, which meets the growing demand for more efficient remote health monitoring. Full article

Esthesioneuroblastoma (ENB) is an uncommon neuroendocrine tumor originating from the olfactory neuroepithelium and accounts for 3–6% of all intranasal tumors [¹]. ENBs can be locally aggressive and cause invasion and destruction of surrounding structures. Histological grading and clinical stage at presentation are highly predictive of survival and especially presence of lymph node and distant metastases are determining prognostic factors [²,³,⁴,⁵]. Thus, reliable imaging is essential in these patients. Conventional imaging modalities for staging ENB are magnetic resonance imaging (MRI) and computed tomography (CT). However, fluorine-18 fluoro-2-deoxy-d-glucose positron emission tomography/CT (¹⁸F-FDG PET/CT) has been reported as a valuable adjunct and was found to upstage 36% of ENB patients compared to conventional imaging [6]. We present a case demonstrating the diagnostic work-up and follow-up with ¹⁸F-FDG PET/CT in a young patient with ENB with a highly atypical clinical presentation. Full article

First rib resection for thoracic outlet syndrome (TOS) is clinically successful and safe in most patients. However, long-term functional outcomes are still insufficiently known. Long-term functional outcome was assessed using a validated questionnaire. A multicenter retrospective cohort study including all patients who underwent operations for TOS from January 2005 until December 2016. Clinical records were reviewed and the long-term functional outcome was assessed by the 11-item version of the Disability of the Arm, Shoulder, and Hand (QuickDASH) questionnaire. Sixty-two cases of TOS in 56 patients were analyzed: 36 neurogenic TOS, 13 arterial TOS, 7 venous TOS, and 6 combined TOS. There was no 30-day mortality. One reoperation because of bleeding was performed and five patients developed a pneumothorax. Survey response was 73% (n = 41) with a follow-up ranging from 1 to 11 years. Complete relief of symptoms was reported postoperatively in 27 patients (54%), symptoms improved in 90%, and the mean QuickDASH score was 22 (range, 0–86). Long-term functional outcome of surgical treatment of TOS was satisfactory, and surgery was beneficial in 90% of patients, with a low risk of severe morbidity. However, the mean QuickDASH scores remain higher compared with the general population, suggesting some sustained functional impairment despite clinical improvement of symptoms. Full article

We report on the development of label-free chemical vapour deposition (CVD) graphene field effect transistor (GFET) immunosensors for the sensitive detection of Human Chorionic Gonadotropin (hCG), a glycoprotein risk biomarker of certain cancers. The GFET sensors were fabricated on Si/SiO₂ substrate using photolithography with evaporated chromium and sputtered gold contacts. GFET channels were functionalised with a linker molecule to an immobile anti-hCG antibody on the surface of graphene. The binding reaction of the antibody with varying concentration levels of hCG antigen demonstrated the limit of detection of the GFET sensors to be below 1 pg/mL using four-probe electrical measurements. We also show that annealing can significantly improve the carrier transport properties of GFETs and shift the Dirac point (Fermi level) with reduced p-doping in back-gated measurements. The developed GFET biosensors are generic and could find applications in a broad range of medical diagnostics in addition to cancer, such as neurodegenerative (Alzheimer’s and Parkinson’s ) and cardiovascular disorders. Full article

Aim: To investigate if the early treatment effects of radiofrequency ablation (RFA) on renal cell carcinoma (RCC) can be detected with dynamic contrast enhanced (DCE)-MRI and to correlate RCC perfusion with RFA treatment time. Materials and methods: 20 patients undergoing RFA of their 21 RCCs were evaluated with DCE-MRI before and at one month after RFA treatment. Perfusion was estimated using the maximum slope technique at two independent sittings. Total RCC blood flow was correlated with total RFA treatment time, tumour location, size and histology. Results: DCE-MRI examinations were successfully evaluated for 21 RCCs (size from 1.3 to 4 cm). Perfusion of the RCCs decreased significantly (p < 0.0001) from a mean of 203 (±80) mL/min/100 mL before RFA to 8.1 (±3.1) mL/min/100 mL after RFA with low intra-observer variability (r ≥ 0.99, p < 0.0001). There was an excellent correlation (r = 0.95) between time to complete ablation and pre-treatment total RCC blood flow. Tumours with an exophytic location exhibit the lowest mean RFA treatment time. Conclusion: DCE-MRI can detect early treatment effects by measuring RCC perfusion before and after RFA. Perfusion significantly decreases in the zone of ablation, suggesting that it may be useful for the assessment of treatment efficacy. Pre-RFA RCC blood flow may be used to predict RFA treatment time. Full article

Tissue perfusion allows for delivery of oxygen and nutrients to tissues, and in the kidneys is also a key determinant of glomerular filtration. Quantification of regional renal perfusion provides a potential window into renal (patho) physiology. However, non-invasive, practical, and robust methods to measure renal perfusion remain elusive, particularly in the clinic. Arterial spin labeling (ASL), a magnetic resonance imaging (MRI) technique, is arguably the only available method with potential to meet all these needs. Recent developments suggest its viability for clinical application. This review addresses several of these developments and discusses remaining challenges with the emphasis on renal imaging in human subjects. Full article