Triple Imaging Research Articles

Negative predictive value of F-18-FDG coincidence PET in patients with Hodgkin's disease and a residual mass after therapy: a retrospective diagnostic test study

Background. The aim of the study was to asses the negative predictive value (NPV) of FDG-PET performed with triple-head coincidence gamma camera after the first-line therapy or salvage therapy in patients with Hodgkin’s disease (HD) compared by a long-term follow-up as a reference standard. Methods. This retrospective diagnostic test study was done at the University Hospital Centre Zagreb between June 2001 and February 2008. The charts of 131 consecutive patients with Hodgkin’s disease were reviewed. Seventy-three consecutive PET-negative patients (median age 28 years; range 12-80 years) with primary or recurrent biopsy confirmed lymphoma after the first-line therapy or salvage therapy were followed-up at least 12 months (median 23 months; range 12-69 months). All already performed 18F-FDG PET scans (using hybrid PET camera with triple head coincidence imaging capability within a few months after the completion of the therapy) were again visually interpreted by two board-certified nuclear medicine physicians who were blinded to any clinical or CT data. The negative predictive value of FDG-PET performed with triple-head coincidence gamma camera (Index test) was compared with a long-term follow-up as a reference standard. Results. Out of 131 patients 73 turned-out to be PET-negative. Of those 73 PET-negative patients, 61 have been scanned after the first-line chemotherapy/radiotherapy, and only 3 of them relapsed in a follow-up (negative predictive value 0.95). Twelve patients with resistant disease have been scanned after the repeated therapy, and 4 of them relapsed in a follow-up period (negative predictive value 0.66). Conclusions. This methodology with a triple-head coincidence gamma camera has a high negative predictive value. A negative PET scan can reassure patients and their doctors that the disease is not active.

Measurement of coincidence timing resolution of scintillation detectors compared to semiconductor detectors to image three-photon positron annihilation

The coincidence timing resolution is a critical parameter for triple coincidence to measure the three photon positron annihilation yield. The yield is inversely proportional to the concentration of oxygen which acts as a quenching agent within the tissue and, therefore, provides important information about the state of the cancerous tumor. A comparison between scintillation and semiconductor detectors with respect to their timing properties for triple coincidence measurements and imaging was carried out. The coincidence timing resolution for example for HPGe detectors was found to vary between 35.4±0.02 and 42.8±0.02 ns. A comparison of all detector characteristics with respect to HPGe is presented.

The role of breast FNAC in diagnosis and clinical management: a survey of current practice

Most participating countries have now adopted a triple assessment approach, i.e. clinical,imaging and pathology, to breast diagnosis, with FNAC as the first-line pathological investigation in both screening and symptomatic populations, with the exception of microcalcifications. Pathologists specialized in cytopathology are best qualified to collect and interpret FNAC samples, but this is not always possible or practical. Radiologists involved in breast imaging should ensure that they have the necessary skills to carry out FNAC under all forms of image guidance. Best results are achieved by a combination of both techniques, as shown in the image-guided FNAC in the presence of the cytopathologist. The majority of European countries use similar reporting systems for breast FNAC (C1-C5), in keeping with European Guidelines for Quality Assurance in Breast Cancer Screening and Diagnosis, although some still prefer descriptive reporting only. When triple assessment is concordant, final treatment may proceed on the basis of FNAC, without a tissue biopsy. ER and PR assessment can be done safely on FNAC material. However, not all institutions may have expertise in doing this. HER-2 protein expression on direct cytological preparations is insufficiently reliable for clinical use, although its use for FISH is possible, if expertise is available. The majority of participants practise a degree of one-stop diagnosis with a cytopathologist present in the out-patient clinic. Formal recognition of the importance of the time spent outside the laboratory, both for cytopathologist and cytotechnologist, is necessary in order to ensure appropriate resourcing. The use of core biopsy (CB) has increased, although not always for evidence-based reasons. CB and FNAC are not mutually exclusive. FNAC should be used in diagnosis of benign, symptomatic lesions and CB in microcalcifications, suspicious FNAC findings and malignancies where radiology cannot guarantee stromal invasion.

Topology of Schwann cells and sympathetic innervation along preglomerular vessels: a confocal microscopic study in protein S100B/EGFP transgenic mice

Schwann cells (Sc), associated axons, and nearby vascular endothelium constitute a functional trilogy of major importance during the development and regrowth of peripheral vascular nerves. The goal of the present study is to provide a technique of triple fluorescence confocal imaging of these cell types along renal preglomerular vessels. We took advantage of a protein S100B/EGFP transgenic mouse to visualize Sc. The endothelium was labeled with an intravenous injection of fluorescently tagged lectin, and after tissue processing, adrenergic nerves were revealed with an antibody against the marker protein synaptophysin. As a validation step, we found that EGFP-positive perivascular cells with prominent cell bodies and extensive, multidirectional cell processes were protein S100B positive. They were identified as Sc and indirectly assumed to be unmyelinated Sc. By contrast, we found strong EGFP expression in proximal epithelial cells and in the epithelium lining thin limbs of Henle. This epithelial fluorescence was not associated with immunoreactive protein S100B and thus corresponded to ectopic EGFP expressions in this mouse strain. Sc were organized in bundles or as a meshwork surrounding the preglomerular vasculature from arcuate arteries to afferent arterioles. No Sc were detected in the medulla. Although most Sc were closely apposed to adrenergic varicosities, many varicosities were not associated with detectable Sc processes. The present technique, and the capacity of confocal microscopy to yield three-dimensional imaging, allow the study of the microtopology of Sc and related sympathetic axons in the renal perivascular interstitium.

Acetylene-vinylidene isomerization in ultrashort intense laser fields studied by triple ion-coincidence momentum imaging

The isomerization of acetylene via hydrogen migration in intense laser fields (8 x 10(14) W/cm2) has been investigated by coincidence momentum imaging of the three-body Coulomb explosion process, C2H2 (3+)-->H+ + C+ + CH+. When ultrashort (9 fs) laser pulses are used, the angle between the momenta of C+ and H+ fragments exhibits a sharp distribution peaked at a small angle ( approximately 20 degrees ), showing that the hydrogen atom remains near the original carbon site in the acetylene configuration. On the other hand, a significantly broad distribution extending to larger momentum angles ( approximately 120 degrees ) is observed when the pulse duration is increased to 35 fs, indicating that the ultrafast isomerization to vinylidene is induced in the longer laser pulse.

Ultrafast imaging of multielectronic dissociative ionization of CO2 in an intense laser field

Momentum vectors of fragment ions produced by the Coulomb explosion of CO2z+ (z = 3–6) in an intense laser field (∼50 fs, 1 × 1015 W cm−2) are determined by the triple coincidence imaging technique. The molecular structure from symmetric and asymmetric explosion channels is reconstructed from the measured momentum vectors. The channel-dependent mean C–O bond length of ⟨r⟩ = 2.14–3.89 Å and the O–C–O bend angle of ⟨θ⟩ = 170–175° confirm substantial deformation of the molecular skeleton during the laser-molecule interaction. The channel-dependent bond length data are qualitatively described using a classical enhanced ionization model. The kinetic energy spectra reveal interesting structure which is attributed to the existence of excited states in the fragment ions.

Human auditory belt areas specialized in sound recognition: a functional magnetic resonance imaging study

The human primary auditory cortex is surrounded by at least six other, anatomically distinct areas that process auditory information. We have investigated their specialization with respect to sound recognition or sound localization with triple epoch functional magnetic resonance imaging paradigm (recognition-localization-rest) in 18 normal individuals. In each study participant, the pattern of selective activation by the recognition or by the localization tasks was superimposed on the map of the nonprimary auditory areas, as identified in previous anatomical studies. Two areas, anterior lateral and anterior areas, were activated bilaterally in significantly more individuals by the recognition than by the localization task. They are proposed to be human homologues of macaque anterolateral auditory belt area.

453 INVITED Tumour stem cells - targeting the root of cancer

Bioluminescence imaging (BLI) has shown to be crucial for monitoring in vivo biological processes. So far, only dual bioluminescence imaging using firefly (Fluc) and Renilla or Gaussia (Gluc) luciferase has been achieved due to the lack of availability of other efficiently expressed luciferases using different substrates. Here, we characterized a codon-optimized luciferase from Vargula hilgendorfii (Vluc) as a reporter for mammalian gene expression. We showed that Vluc can be multiplexed with Gluc and Fluc for sequential imaging of three distinct cellular phenomena in the same biological system using vargulin, coelenterazine, and D-luciferin substrates, respectively. We applied this triple imaging system to monitor the effect of soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) delivered using an adeno-associated viral vector (AAV) on brain tumors in mice. Vluc imaging showed efficient sTRAIL gene delivery to the brain, while Fluc imaging revealed a robust antiglioma therapy. Further, nuclear factor-κB (NF-κB) activation in response to sTRAIL binding to glioma cells death receptors was monitored by Gluc imaging. This work is the first demonstration of trimodal in vivo bioluminescence imaging and will have a broad applicability in many different fields including immunology, oncology, virology, and neuroscience.

Performance of triple coincidence imaging as an addition to dedicated PET

In this work, we investigate the performance of semiconductor detectors imaging capabilities in three-photon annihilation processes in order to combine this novel imaging modality with conventional positron emission tomography. The spatial resolution is studied as a function of detector positions and selected energy window. This was measured from different experimental arrangements and found to be in the range between 3.3–3.9 cm with a mean of 3.5±0.1 cm. Scatter and random events, coincidence timing resolution and count rate performance are discussed.

Triple Arterial Phase Dynamic MRI with Sensitivity Encoding for Hypervascular Hepatocellular Carcinoma: Comparison of the Diagnostic Accuracy Among the Early, Middle, Late, and Whole Triple Arterial Phase Imaging

We assessed and compared the diagnostic accuracy of the early, middle, late, and whole triple arterial phase MRI with sensitivity encoding (SENSE) for the detection of hypervascular hepatocellular carcinoma (HCC). Thirty-one patients with 102 HCCs underwent dynamic MRI with SENSE. The findings of CT examinations, combined with those of visceral angiography or histopathologic examination, were used as the gold standard. After acquisition of T1- and T2-weighted images, gadolinium-enhanced triple arterial, portal, and delayed phase images were obtained. Acquisition of the triple arterial phase imaging was started at the timing of peak aortic enhancement and completed within a single breath-hold. Acquisition time for each phase was 8.4 sec. Four image sets including the early, middle, late, and whole triple arterial phase imaging were interpreted separately by four observers. The mean values of area under alternative-free-response receiver operating characteristic (AFROC) curve and of sensitivity were compared among the four image sets. The mean values of area under AFROC curve were 0.52, 0.66, 0.53, and 0.68 and of sensitivity were 45%, 64%, 48%, and 65% for the image sets with the early, middle, late, and whole triple arterial phase imaging, respectively. Both mean values were significantly higher for the image sets with the middle and whole triple arterial phase imaging than for those with the early and late arterial phase imaging. The middle arterial phase imaging with k-space centered at 12.6 sec after the peak aortic enhancement was optimal for detecting HCC and showed diagnostic accuracy equivalent to that of the whole triple arterial phase imaging.

Detecting and Quantifying Colocalization of Cell Surface Molecules by Single Particle Fluorescence Imaging

Single particle fluorescence imaging (SPFI) uses the high sensitivity of fluorescence to visualize individual molecules that have been selectively labeled with small fluorescent particles. The positions of particles are determined by fitting the intensity profile of their images to a 2-D Gaussian function. We have exploited the positional information obtained from SPFI to develop a method for detecting colocalization of cell surface molecules. This involves labeling two different molecules with different colored fluorophores and determining their positions separately by dual wavelength imaging. The images are analyzed to quantify the overlap of the particle images and hence determine the extent of colocalization of the labeled molecules. Simulated images and experiments with a model system are used to investigate the extent to which colocalization occurs from chance proximity of randomly distributed molecules. A method of correcting for positional shifts that result from chromatic aberration is presented. The technique provides quantification of the extent of colocalization and can detect whether colocalized molecules occur singly or in clusters. We have obtained preliminary data for colocalization of molecules on intact cells. Cells often exhibit particulate autofluorescence that can interfere with the measurements; a method for overcoming this problem by triple wavelength imaging is described.

Ganglioside Glycosyltransferases Organize in Distinct Multienzyme Complexes in CHO-K1 Cells

The synthesis of gangliosides is compartmentalized in the Golgi complex. In most cells, glycosylation of LacCer, GM3, and GD3 to form higher order species (GA2, GM2, GD2, GM1, GD1b) is displaced toward the most distal aspects of the Golgi and the trans-Golgi network, where the involved transferases (GalNAcT and GalT2) form physical and functional associations. Glycosylation of the simple species LacCer, GM3, and GD3, on the other hand, is displaced toward more proximal Golgi compartments, and we investigate here whether the involved transferases (GalT1, SialT1, and SialT2) share the property of forming physical associations. Co-immunoprecipitation experiments from membranes of CHO-K1 cells expressing epitope-tagged versions of these enzymes indicate that GalT1, SialT1, and SialT2 associate physically in a SialT1-dependent manner and that their N-terminal domains participate in these interactions. Microscopic fluorescence resonance energy transfer and fluorescence recovery after photobleaching in living cells confirmed the interactions, and in addition to showing a Golgi apparatus localization of the complexes, mapped their formation to the endoplasmic reticulum. Neither co-immunoprecipitation nor fluorescence resonance energy transfer detected interactions between either GalT2 or GalNAcT and GalT1 or SialT1 or SialT2. These results, and triple color imaging of Golgi-derived microvesicles in nocodazole-treated cells, suggest that ganglioside synthesis is organized in distinct units each formed by associations of particular glycosyltransferases, which concentrate in different sub-Golgi compartments.

Evaluation of optimal timing of arterial phase imaging for the detection of hypervascular hepatocellular carcinoma by using triple arterial phase imaging with multidetector-row helical computed tomography.

We evaluated the optimal timing of arterial phase imaging for detection of hypervascular hepatocellular carcinoma by using triple arterial phase imaging with multidetector-row helical computed tomography. Forty-nine patients with 90 hypervascular hepatocellular carcinomas (3 to 50 mm in diameter; mean, 18.7 mm) underwent triple arterial phase imaging of the whole liver using a multidetector-row helical computed tomography. At 20 seconds, 30 seconds, and 40 seconds after intravenous administration of 100 mL of 300 mgI/mL of nonionic contrast medium at a rate of 4 mL/s, early, middle, and late arterial phase images were obtained serially during a single breath-hold with an interscan delay of 5 seconds. Detector-row configurations of 4 mm x 4, scan pitch of 5.5, and scan time of 5 seconds for each phase were used. Forty prospective reconstruction images of 5-mm thickness for each phase were obtained. The images from each phase were interpreted separately for detection of hypervascular hepatocellular carcinoma by 3 observers independently who were unaware of tumor burden in the liver. Sensitivity, positive predictive value, and area under the receiver operating characteristic curve values for each arterial phase were calculated and compared statistically. The mean sensitivity and positive predictive values for hypervascular hepatocellular carcinoma diagnosis of blind readers were 37% and 87% for the early arterial phase, 73% and 85% for the middle arterial phase, and 49% and 81% for the late arterial phase, respectively. The middle arterial phase imaging showed significantly superior sensitivity compared with the early and late arterial phase for detecting hepatocellular carcinoma (P < 0.05). Mean area under the receiver operating characteristic curve value of the middle arterial phase imaging (0.84) was significantly higher that that of the early (0.56) or late arterial phase (0.62; P < 0.05). If a single arterial phase is used for diagnosis of hypervascular hepatocellular carcinoma, the middle phase (delay time of 30 seconds) is optimal.

An inverse problem for three-dimensional x-ray scatter/transmission imaging

The mathematical formulation and numerical aspects of the inverse problem of athree-dimensional (3D) x-ray imaging method are introduced. The imagingmethod relies on measuring radiation scattered at two directions orthogonal toan incident beam that scans one side of the object, in addition to thetraditionally recorded transmitted radiation. From this set of measurements, theinverse problem reconstructs three images: the attenuation coefficient at theincident energy, the attenuation coefficient at a scattering energy and thescattering coefficients (with the latter directly related to the electron, andhence mass density). The algorithms for this triple imaging process arepresented and their numerical characteristics are discussed. With the aidof regularization and an iterative learning process, stable and boundedsolutions are obtained. This 3D image-reconstruction process was able torecover the domain of interest and distinguish between different materials.

Sequential three-body Coulomb explosion of CS 2 in intense laser fields appearing in momentum correlation map

The three-body Coulomb explosion process of CS 2 in intense laser fields ( 60 fs , 0.36×10 15 W/ cm 2 ), CS 2 3+→S ++C ++S +, is studied by the triple coincidence momentum imaging of the atomic fragment ions. The set of the observed momentum vectors of the fragment ions determined for respective explosion events exhibits a clear trajectory originating from the rotational motion of an intermediate CS 2+ ion, formed in a sequential explosion process of CS 2 3+ prior to the complete three-body fragmentation. The contribution of the sequential pathway to the overall three-body explosion process is estimated to be 17(1)%.

Serial gadolinium-DTPA of spinal cord MRI in multiple sclerosis: triple vs. single dose

We compared the sensitivity of single and triple dose Gd-DTPA magnetic resonance imaging (MRI) in detecting enhancing lesions in the spinal cord (SC) from 15 patients with multiple sclerosis (MS). The patients were examined monthly on four occasions. We detected two enhancing lesions in two of 15 (13%) patients when a single dose of Gd-DTPA was used. No additional lesions were detected when a triple dose of Gd-DTPA was used. These results 1) confirm that enhanced spinal cord imaging does not significantly increase the detection of active lesions in MS, 2) they do not support the general application of triple dose Gd-DTPA when examining the SC but 3) suggest that further studies taking into account SC symptoms are necessary.

Motion detection in triple scan SPECT imaging

An algorithm to automatically detect and eliminate motion in projection data from triple scan SPECT imaging is proposed. The approach relies on a protocol where each head acquires projections over a full 360 degrees orbit rather than over the conventional 120 degrees partial orbit. Projection acquisition times are reduced to one third of that used for the partial orbit protocol to keep comparable total scan times. This protocol permits the acquisition of three full sets of SPECT data which can be adequately combined in order to reconstitute a motion-free set of projection data. Cross-correlation of the projection sets as a function of angle are used to detect motion. Plateaus of high correlation are estimated and matched in order to identify projections corresponding to the same position of a subject throughout a study. The motion correction algorithm was tested on experimental data obtained by manually moving a cardiac phantom at different times. In all cases, it was possible to reconstitute the evolution of the motion during the study. When no motion occurred during an interval equal to at least one third of the total acquisition time, high correlation plateaus were identified and complete sets of consistent projections were assembled from the longest matching plateaus. When more frequent motion occurred, an averaging of the three sets provided a means to improve the quality of the reconstructed slices compared to conventional imaging protocol.

Triple dose of gadolinium-DTPA increases the sensitivity of spinal cord MRI in detecting enhancing lesions in multiple sclerosis.

We compared the sensitivity of single and triple dose Gd-DTPA magnetic resonance imaging (MRI) in detecting enhancing lesions in the spinal cord of 13 patients with multiple sclerosis (MS). We detected two enhancing lesions in two of 13 (15%) patients when the single dose of Gd-DTPA was used and 12 lesions in five of 13 (38%) patients when the triple dose of Gd-DTPA was used. These results suggest that: (1) the use of triple dose increases the sensitivity of spinal cord MRI when studying relapsing-remitting or secondary progressive MS patients, (2) triple dose Gd-DTPA enhanced of the spinal cord MRI might be useful in monitoring disease activity in patients with MS.

Triple quantum sodium imaging of articular cartilage.

Triple quantum (TQ) sodium imaging of bovine articular cartilage is presented. True triple quantum imaging sequence was modified to incorporate asymmetric echo acquisition. Triple quantum signal expression in the presence of residual quadrupolar interaction is presented. The filtering capability of the sequence is first demonstrated on an agarose phantom. Both single and triple quantum images of articular cartilage are compared. The TQ image shows non-zero signal intensity solely from cartilage, indicating complete suppression of signals from bone marrow and saline. The advantages of TQ imaging of articular cartilage, its feasibility in in vivo situations and further improvements in SNR are described.

Imaging of Cerebral Metastases

MR imaging with intravenous gadolinium has greatly enhanced our ability to detect and delineate intracranial metastases as well as to differentiate them from other disease processes. Techniques such as magnetization transfer and triple dose gadolinium imaging have further improved lesion detection. Consideration of these radiologic techniques, including the issues and controversies of screening and cost effectiveness, suggests a reasonable approach to imaging patients with possible intracranial metastases. Newer modalities such as echo planar imaging, spectroscopy, PET, and SPECT, may in the future, prove to be very useful in the evaluation of patients with intracranial metastases. Proper imaging is also critical to appropriate diagnosis and management of meningeal metastases, calvarial metastases, and paraneoplastic disease.