Nigel G. Anderson

Dual- and multi-energy CT: approach to functional imaging

The energy spectrum of X-ray photons after passage through an absorber contains information about its elemental composition. Thus, tissue characterisation becomes feasible provided that absorption characteristics can be measured or differentiated. Dual-energy CT uses two X-ray spectra enabling material differentiation by analysing material-dependent photo-electric and Compton effects. Elemental concentrations can thereby be determined using three-material decomposition algorithms. In comparison to dual-energy CT used in clinical practice, recently developed energy-sensitive photon-counting detectors sample the material-specific attenuation curves at multiple energy levels and within narrow energy bands; the latter allows the detection of element-specific, k-edge discontinuities of the photo-electric cross section. Multi-energy CT imaging therefore is able to concurrently identify multiple materials with increased accuracy. These specific data on material distribution provide information beyond morphological CT, and approach functional imaging. This article reviews the principles of dual- and multi-energy CT imaging, hardware approaches and clinical applications.

Sonographic estimation of fetal weight: comparison of bias, precision and consistency using 12 different formulae.

To determine the major sources of error in ultrasonographic assessment of fetal weight and whether they have changed over the last decade.

Vesicoureteric reflux in the newborn : relationship to fetal renal pelvic diameter

Abstract. There has been a low yield of primary vesicoureteric reflux (VUR) from screening the fetal urinary tract during obstetric sonography. We sought to determine whether changing the cut-off level of fetal renal pelvic diameter from 10 mm to 4 mm would improve the yield of VUR. In a prospective community-based study, a fetal renal pelvic diameter of 4 mm or more on a transverse view of the fetal renal hilum at obstetric sonography after 16 weeks’ gestation was found in 426 fetuses from 9,800 consecutive pregnancies. After birth, renal sonography was performed on 386 of the 426 babies. Of the 386 babies, 264 (187 boys) had a voiding cystourethrogram (VCUG) at a mean age of 9 weeks. Primary VUR was detected in 33 (16 boys) of the 264 infants (13%), and secondary VUR in another 5 (2%). Only 5 of the 33 (15%) babies with primary VUR would have been detected if a cut-off point of 10 mm for fetal renal pelvic diameter had been used. The prevalence of reflux was similar at each cut-off level of antenatal renal pelvic diameter from 4 to 10 mm. Neither calyceal nor ureteric dilatation was helpful in differentiating those with from those without VUR. The postnatal renal sonogram did not distinguish whether reflux was present or not. More infants with primary VUR, particularly girls, were found by changing the cut-off point for fetal renal pelvic diameter from 10 mm to 4 mm, and performing a VCUG on all such infants even if the postnatal renal sonogram was normal. Of the 33 infants with primary VUR, 9 (27%, 5 boys) had an abnormal dimercaptosuccinic acid scan. Our findings support the screening of the obstetric population for a fetal renal pelvic diameter of 4 mm or more, and then investigating the infants for VUR after birth.

Outcome of primary vesicoureteric reflux detected following fetal renal pelvic dilatation

Objective: Postnatal investigation of mild degrees of fetal hydronephrosis has allowed subsequent detection of infants with vesicoureteric reflux (VUR). This study was designed to provide short to medium term information on such infants who had primary VUR, the rates of renal damage and progression over time, the risk factors for such damage and to compare the characteristics of those who had mild dilatation of the fetal renal pelvis (4–9 mm) with those who had moderate–severe dilatation (≥ 10 mm).

Toward quantifying the composition of soft tissues by spectral CT with Medipix3

PURPOSE To determine the potential of spectral computed tomography (CT) with Medipix3 for quantifying fat, calcium, and iron in soft tissues within small animal models and surgical specimens of diseases such as fatty liver (metabolic syndrome) and unstable atherosclerosis. METHODS The spectroscopic method was applied to tomographic data acquired using a micro-CT system incorporating a Medipix3 detector array with silicon sensor layer and microfocus x-ray tube operating at 50 kVp. A 10 mm diameter perspex phantom containing a fat surrogate (sunflower oil) and aqueous solutions of ferric nitrate, calcium chloride, and iodine was imaged with multiple energy bins. The authors used the spectroscopic characteristics of the CT number to establish a basis for the decomposition of soft tissue components. The potential of the method of constrained least squares for quantifying different sets of materials was evaluated in terms of information entropy and degrees of freedom, with and without the use of a volume conservation constraint. The measurement performance was evaluated quantitatively using atheroma and mouse equivalent phantoms. Finally the decomposition method was assessed qualitatively using a euthanized mouse and an excised human atherosclerotic plaque. RESULTS Spectral CT measurements of a phantom containing tissue surrogates confirmed the ability to distinguish these materials by the spectroscopic characteristics of their CT number. The assessment of performance potential in terms of information entropy and degrees of freedom indicated that certain sets of up to three materials could be decomposed by the method of constrained least squares. However, there was insufficient information within the data set to distinguish calcium from iron within soft tissues. The quantification of calcium concentration and fat mass fraction within atheroma and mouse equivalent phantoms by spectral CT correlated well with the nominal values (R(2) = 0.990 and R(2) = 0.985, respectively). In the euthanized mouse and excised human atherosclerotic plaque, regions of calcium and fat were appropriately decomposed according to their spectroscopic characteristics. CONCLUSIONS Spectral CT, using the Medipix3 detector and silicon sensor layer, can quantify certain sets of up to three materials using the proposed method of constrained least squares. The system has some ability to independently distinguish calcium, fat, and water, and these have been quantified within phantom equivalents of fatty liver and atheroma. In this configuration, spectral CT cannot distinguish iron from calcium within soft tissues.

Relationship of isolated fetal intracardiac echogenic focus to trisomy 21 at the mid‐trimester sonogram in women younger than 35 years

To determine whether an isolated echogenic intracardiac focus in the fetal heart in the mid‐trimester (16–24 weeks) in women aged 18–34 years of age is associated with trisomy 21.

Energy Calibration of the Pixels of Spectral X-ray Detectors

The energy information acquired using spectral X-ray detectors allows noninvasive identification and characterization of chemical components of a material. To achieve this, it is important that the energy response of the detector is calibrated. The established techniques for energy calibration are not practical for routine use in pre-clinical or clinical research environment. This is due to the requirements of using monochromatic radiation sources such as synchrotron, radio-isotopes, and prohibitively long time needed to set up the equipment and make measurements. To address these limitations, we have developed an automated technique for calibrating the energy response of the pixels in a spectral X-ray detector that runs with minimal user intervention. This technique uses the X-ray tube voltage (kVp) as a reference energy, which is stepped through an energy range of interest. This technique locates the energy threshold where a pixel transitions from not-counting (off) to counting (on). Similarly, we have developed a technique for calibrating the energy response of individual pixels using X-ray fluorescence generated by metallic targets directly irradiated with polychromatic X-rays, and additionally γ-rays from 241Am. This technique was used to measure the energy response of individual pixels in CdTe-Medipix3RX by characterizing noise performance, threshold dispersion, gain variation and spectral resolution. The comparison of these two techniques shows the energy difference of 1 keV at 59.5 keV which is less than the spectral resolution of the detector (full-width at half-maximum of 8 keV at 59.5 keV). Both techniques can be used as quality control tools in a pre-clinical multi-energy CT scanner using spectral X-ray detectors.

Clinical applications of spectral molecular imaging: potential and challenges

Spectral molecular imaging is a new X-ray-based imaging technology providing highly specific 3D imaging at high spatial resolution that has the potential to measure disease activity and response to treatment noninvasively. The ability to identify and quantify components of tissue and biomarkers of disease activity derive from the properties of the photon-processing detector. Multiple narrow sections of the energy spectrum are sampled simultaneously, providing a range of energy dependent Hounsfield units. As each material has a specific measurable X-ray spectrum, spectroscopic imaging allows for multiple materials to be quantified and differentiated from each other simultaneously. The technology, currently in its infancy, is set to grow rapidly, much as magnetic resonance did. The critical clinical applications have not yet been established, but it is likely to play a major role in identifying and directing treatment for unstable atherosclerotic plaque, assessing activity and response to treatment of a range of inflammatory diseases, and monitoring biomarkers of cancer and its treatment. If combined with Positron-emission tomography (PET), spectral molecular imaging could have a far greater effective role in cancer diagnosis and treatment monitoring than PET-CT does at present. It is currently used for small animal and specimen imaging. There are many challenges to be overcome before spectral imaging can be introduced into clinical medicine - these include technological improvements to detector design, bonding to the semiconductor layer, image reconstruction and display software, identifying which biomarkers are of most relevance to the disease in question, and accelerating drug discovery enabled by the new capabilities provided by spectral imaging.

Distal Ureteral Calculi: US Follow-up

PURPOSE To assess accuracy of ultrasonographic (US) follow-up of distal ureteral calculi by using computed tomography (CT) and conventional radiography (kidneys, ureters, and bladder) as reference standards. MATERIALS AND METHODS The study was approved by the Regional Ethics Committee, and written informed consent was obtained. One hundred fifty-eight patients with CT-diagnosed symptomatic ureteral calculi, for whom follow-up imaging was ordered, were enrolled from February 2006 to December 2008. Six were excluded, having not met study entry criteria, with 121 men (mean age, 49 years; range, 20-91 years) and 31 women (mean age, 44 years; range, 34-77 years) completing the protocol with adequate reference standard imaging. Targeted transabdominal US occurred coincidently with follow-up CT (n = 92) or radiography (n = 60), with US evaluation prospectively compared considering sensitivity and specificity. Statistical analysis was performed with a χ(2) test, t test, or paired t test, as appropriate. RESULTS Results of nine US examinations were nondiagnostic because of inadequate ureteral visualization, and among these, two cases showed residual distal calculi. Of the remaining 143 patients, 33 had residual distal calculi, all visualized with US. There was a single false-positive study, giving sensitivity, including nondiagnostic US examinations, of 94.3% (95% confidence interval [CI]: 80.8%, 99.3%) and specificity of 99.1% (95% CI: 95.3%, 100%). All calculi appeared hyperechoic with posterior acoustic shadowing. Additional diagnostic features included presence of a hypoechoic rim and Doppler twinkle artifact. Mean stone length was 7.2 mm ± 2.6 (standard deviation) (range, 4-18 mm). Mean ureteral length visualized was 36.4 mm (range, 12-77 mm), with calculi positioned at a mean of 13.1 mm ± 11.2 (range, 0-40 mm) from the ureterovesical junction (UVJ). Nondiagnostic results were more likely with bladder volume of 110 mL or less (eight [16%] of 50 vs one [1%] of 102, P = .0009). CONCLUSION Ureteral calculi within 35 mm of the UVJ can be accurately followed-up by using transabdominal US, which substantially reduces patient radiation burden.

Spectroscopic biomedical imaging with the Medipix2 detector

This study confirms that the Medipix2 x-ray detector enables spectroscopic bio-medical plain radiography. We show that the detector has the potential to provide new, useful information beyond the limited spectroscopic information of modern dual-energy computed tomography (CT) scanners. Full spectroscopic 3D-imaging is likely to be the next major technological advance in computed tomography, moving the modality towards molecular imaging applications. This paper focuses on the enabling technology which allows spectroscopic data collection and why this information is useful. In this preliminary study we acquired the first spectroscopic images of human tissue and other biological samples obtained using the Medipix2 detector. The images presented here include the clear resolution of the 1.4mm long distal phalanx of a 20-week-old miscarried foetus, showing clear energy-dependent variations. The opportunities for further research using the forthcoming Medipix3 detector are discussed and a prototype spectroscopic CT scanner (MARS, Medipix All Resolution System) is briefly described.