Standardization in Quantitative Imaging: A Multicenter Comparison of Radiomic Features from Different Software Packages on Digital Reference Objects and Patient Data Sets.

Radiomic features are being increasingly studied for clinical applications. We aimed to assess the agreement among radiomic features when computed by several groups by using different software packages under very tightly controlled conditions, which included standardized feature definitions and common image data sets. Ten sites (9 from the NCI's Quantitative Imaging Network] positron emission tomography-computed tomography working group plus one site from outside that group) participated in this project. Nine common quantitative imaging features were selected for comparison including features that describe morphology, intensity, shape, and texture. The common image data sets were: three 3D digital reference objects (DROs) and 10 patient image scans from the Lung Image Database Consortium data set using a specific lesion in each scan. Each object (DRO or lesion) was accompanied by an already-defined volume of interest, from which the features were calculated. Feature values for each object (DRO or lesion) were reported. The coefficient of variation (CV), expressed as a percentage, was calculated across software packages for each feature on each object. Thirteen sets of results were obtained for the DROs and patient data sets. Five of the 9 features showed excellent agreement with CV < 1%; 1 feature had moderate agreement (CV < 10%), and 3 features had larger variations (CV ≥ 10%) even after attempts at harmonization of feature calculations. This work highlights the value of feature definition standardization as well as the need to further clarify definitions for some features.

Pulmonary arterial hypertension associated to connective tissue diseases.

Pulmonary arterial hypertension is a well-known complication of connective tissue diseases such as systemic sclerosis, systemic lupus erythematosus, mixed connective tissue diseases, and to a lesser extent, rheumatoid arthritis, dermatopolymyositis and primary Sjögren's syndrome. In these patients, pulmonary hypertension may occur in association with left heart disease, interstitial fibrosis or as a result of a isolated pulmonary arteriopathy. The incidence of pulmonary arterial hypertension in the limited form of systemic sclerosis is about 10%. The pathophysiologic mechanisms leading to pulmonary arterial hypertension remain unknown. Symptoms and clinical presentation are very similar to idiopathic pulmonary arterial hypertension but mortality was confirmed to be higher. Echocardiography is the reference investigation for the detection of pulmonary arterial hypertension but the results should be confirmed by right heart catheterization. Treatment appears more complex as compared to idiopathic pulmonary arterial hypertension. Intravenous epoprostenol therapy has been shown to be effective in a special trail. Also, the endothelin receptor antagonists bosentan and sitaxentan, the phosphodyesterase-type-5 sildenafil and subcutaneous treprostinil have shown favourable results.

Novel observations with FDOPA-PET imaging after early nigrostriatal damage.

Striatal 6-[18F]fluoro-L-DOPA (FDOPA) kinetic rate constants were measured by positron emission tomography (PET) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated squirrel monkeys. After scanning, stereological counts of dopaminergic neurons were done in substantia nigra, and dopamine (DA) and metabolite concentrations were determined in the caudate, putamen, and substantia nigra. Graded doses of MPTP produced animals with mild to moderate reductions (10-35%) in dopaminergic neurons, where the percent of cell loss was proportional to the amount of MPTP given. Striatal DA and metabolite concentrations were relatively unchanged in animals given 1.0 and 1.5 mg/kg of MPTP, but were significantly reduced after 2.0 mg/kg of MPTP. All animals injected with a single dose of MPTP showed no overt signs of parkinsonism. In contrast, DA and metabolite concentrations in the substantia nigra were significantly reduced for all MPTP-treated animals. Reduction of dopaminergic indices in the substantia nigra did not parallel reductions in the striatum, indicating differential sensitivity of the nigrostriatal pathway to the neurotoxic effects of MPTP. The percent change in FDOPA uptake (Ki) and decarboyxlation (k3) after MPTP showed significant positive correlations to striatal DA levels, but not to the number of dopaminergic neurons. This suggests that FDOPA is a good index of striatal DA levels.

Safety of MRI-guided endovascular guidewire applications.

Magnetic radiofrequency (RF) fields applied during magnetic resonance imaging (MRI) may induce heating in devices made from conductive materials. The present paper reports on theoretical and experimental studies on the RF heating resonance phenomenon of an endovascular guidewire. A nitinol-based guidewire was inserted into a vessel phantom and imaged at 1.5 and 0.2 T with continuous temperature monitoring at the guidewire tip. The heating effects due to different experimental settings were examined. A model is developed for the resonant current and the associated electric field produced by the guidewire acting as an antenna. Temperature increases of up to 17 degrees C were measured while imaging the guidewire at an off-center position in the 1.5 T MR system. Power absorption produced by the resonating wire decreased as the repetition time was increased. No temperature rise was measured at 0.2 T. Considering the potential utility of low-field, open MR systems for MRI-guided endovascular interventions, it is important to be aware of the safety of such applications.

Striatal kinetic modeling of FDOPA with a cerebellar-derived constraint on the distribution of volume of 30MFD: a PET investigation using non-human primates.

The peripherally born metabolite of FDOPA, 3-O-Methyl-FDOPA (3OMFD), crosses the blood-brain barrier, thus complicating positron emission tomography-FDOPA (PET-FDOPA) data analysis. In previous reports the distribution volume (DV) of 3OMFD was constrained to unity. We have recently shown that the forward transport rate-constant of FDOPA (K(S1)) and the cerebellum-to-plasma ratio (C(b)/C(p)), a measure for the DV of 3OMFD, are functions of plasma large neutral amino acid (LNAA) concentration. Given large interstudy and intersubject differences in plasma LNAA levels, variations in the DV of 3OMFD are significant. In this report, the authors propose a constraint on the DV of 3OMFD that accounts for these variations. Dynamic PET-FDOPA scans were performed on 12 squirrel monkeys and 12 vervet monkeys. Two sets of constraints were employed on the compartmental model--M1 or M2. In M1, the striatal DV of 3OMFD was constrained to unity; in M2, the striatal DV of 3OMFD was constrained to an estimate derived from the cerebellum. Striatal and cerebellar time-activity curves were fitted using FDOPA and 3OMFD plasma input functions. The estimate of K(S1) and that of the compartmental FDOPA uptake-constant (K(i)), both obtained using M2, were adjusted to values corresponding to average LNAA levels. Finally, K(i) was compared with the graphical uptake-constant (PK(j)). With the use of constraint M2, intersubject variability of squirrel monkey k(S3) and K(i) was reduced by 45% and 53%, respectively; and for vervet monkeys, by 54% and 44%, respectively. Intersubject variability of K(1) and K(i) was further reduced after correction for variations in intersubject plasma LNAA levels (for squirrel monkeys, by 67% and 41%; for vervet monkeys, by 40% and 36%, respectively). K(i) correlation to PK(i) was enhanced to identity. Finally, average cerebellar k(C2) estimates were more than 2.5-fold higher than striatal k(S2) estimates (P < 0.0001). In modeling of PET-FDOPA data, it cannot be assumed that the DV of 3OMFD is unity. The cerebellar-derived constraint furnishes a reliable estimate for the DV of 3OMFD. Invoking the constraint and correcting for variations in plasma LNAA significantly reduced interstudy and intersubject variations in parameter estimates.

Magnetic resonance imaging-guided neurosurgery in the magnetic fringe fields: the next step in neuronavigation.

OBJECTIVE: We describe the development of an alternative approach to intraoperative magnetic resonance imaging (iMR)-guided neurosurgery and report our initial experience with 22 craniotomies and 16 brain biopsies. The advantages and disadvantages of each approach are examined. METHODS: An iMR suite houses a 0.2-T open configuration system (Siemens Medical Systems, Erlangen, Germany) and is equipped with anesthetic gases and a magnetic resonance imaging (MRI)-compatible anesthesia machine and monitor. Standard operating instruments and equipment were tested for safety and compatibility in the magnetic fringe fields surrounding the open MRI system. We then performed brain biopsies and craniotomies in the iMR suite. RESULTS: Standard operating equipment functioned properly in the 0.5- to 10-mT zone and was not affected by the magnet's attractive force. Twenty-two craniotomies and 16 brain biopsies were performed in the interventional suite, using serial intraoperative MRI guidance, without injury to patients or operating room staff. CONCLUSION: Full neurosurgical procedures may be performed in the weak fringe fields surrounding an MRI system, using standard operating room equipment. This approach to iMR-guided neurosurgery offers a significant cost advantage over retrofitting an entire operative suite with "MRI-compatible" surgical equipment. The surgeon's familiarity with standard equipment and the reliability of the equipment are additional advantages. Neurosurgery in the fringe fields allows the neurosurgeon to utilize serial MRI with a minimum of inconvenience, disruption, and change to the standard neurosurgical procedure. Serial intraoperative imaging to visualize the changes in the brain that are associated with neurosurgical intervention seems to enhance the ability to safely and effectively accomplish neurosurgical goals.

Nigrostriatal reduction of aromatic L-amino acid decarboxylase activity in MPTP-treated squirrel monkeys: in vivo and in vitro investigations.

Aromatic L-amino acid decarboxylase (AAAD) activity was examined in vivo with positron emission tomography (PET) using 6-[18F]fluoro-L-DOPA (FDOPA) in squirrel monkeys lesioned with graded doses of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In vitro biochemical determinations of AAAD activity in caudate, putamen, substantia nigra, and nucleus accumbens were performed in the same animals to establish a direct comparison of in vivo and in vitro measurements. In vivo and in vitro AAAD activities in caudate/ putamen were substantially reduced in animals treated with the highest dose of MPTP (2.0 mg/kg). The percent change in the striatal FDOPA uptake (K(i)) and decarboxylation rate constant (k3) values resulting from MPTP treatment showed highly significant correlations with in vitro-determined AAAD activities. However, decarboxylase rates within individual animals presented as approximately 10-fold difference between in vivo and in vitro values. Lower in vivo k3 measurements may be attributed to several possibilities, including transport restrictions limiting substrate availability to AAAD within the neuron. In addition, reductions in AAAD activity in the substantia nigra did not parallel reductions in AAAD activity within the striatum, supporting the notion of a nonlinear relationship between nigrostriatal cell degeneration and terminal losses. This work further explores the role of AAAD in Parkinson's disease, a more important factor than previously thought.

MRI of thermally denatured blood: methemoglobin formation and relaxation effects.

Focal regions of T1-shortening have been observed in magnetic resonance imaging (MRI)-monitored thermal ablations of perfused tissues. The aims of this study were two-fold: to find evidence for heat-induced conversion of hemoglobin (Hb) to methemoglobin (mHb), and to investigate the effects of heat treatment of in-vitro blood components upon their MR relaxation times. Spectrophotometric studies were performed to confirm the heat-induced formation of methemoglobin. Preparations of whole and fractionated blood, previously submitted to elevated temperatures of 40 degrees C to 80 degrees C, were imaged and the relaxation times were calculated. Optical absorption spectra of samples containing free Hb, heated to 60 degrees C, showed increased light absorption at 630 nm, evident of mHb presence. Short T1 values in whole blood (1.13 s) and packed red blood cell (0.65 s) compartments, heated at 60 degrees C, compared to their baseline values (1.62 s and 0.83 s, respectively), were attributed to mHb formation. In relation to MRI-guided thermal interventions, these results suggest a possible explanation for observation of hyperintense regions on T1-weighted images.

A study of artefacts in simultaneous PET and MR imaging using a prototype MR compatible PET scanner.

We have assessed the possibility of artefacts that can arise in attempting to perform simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) using a small prototype MR compatible PET scanner (McPET). In these experiments, we examine MR images for any major artefacts or loss in image quality due to inhomogeneities in the magnetic field, radiofrequency interference or susceptibility effects caused by operation of the PET system inside the MR scanner. In addition, possible artefacts in the PET images caused by the static and time-varying magnetic fields or radiofrequency interference from the MR system were investigated. Biological tissue and a T2-weighted spin echo sequence were used to examine susceptibility artefacts due to components of the McPET scanner (scintillator, optical fibres) situated in the MR field of view. A range of commonly used MR pulse sequences was studied while acquiring PET data to look for possible artefacts in either the PET or MR images. Other than a small loss in signal-to-noise using gradient echo sequences, there was no significant interaction between the two imaging systems. Simultaneous PET and MR imaging of simple phantoms was also carried out in different MR systems with field strengths ranging from 0.2 to 4.7 T. The results of these studies demonstrate that it is possible to acquire PET and MR images simultaneously, without any significant artefacts or loss in image quality, using our prototype MR compatible PET scanner.

Teleradiology in the operating room of the future.

Recent advances in magnetic resonance imaging (MRI) are rapidly making this modality the imaging method of choice for image-guided neurosurgical operations. However, to be ready for its prime time in the operating room (OR), utilization of MRI in the OR requires development of better techniques for image-guided navigation, as well as interactive real-time teleradiologic methods that will allow tele-collaboration between the surgeon and the radiologist. This presentation describes our work in progress toward achievement of teleradiology in the OR.

Contemporaneous positron emission tomography and MR imaging at 1.5 T.

Simultaneous acquisition of positron emission tomography (PET) and magnetic resonance (MR) images using an MR-compatible PET system will obviate the need for image registration and will allow unique studies of structure and function of living organisms in one setting. Here we report on simultaneous acquisition of PET and MR images on a clinical 1.5 T system using a 54 mm diameter prototype MR-compatible PET system (McPET). Phantom experiments were performed in order to determine the effect of the McPET system on MR images. The results demonstrated the system to be fully MR compatible, in both its detector head construction and operation. The McPET construction offers a promising method for design of a large-scale MR-compatible PET system that will be useful in functional studies of the brain.

Intra-arterial Cereport (RMP-7) and carboplatin: a dose escalation study for recurrent malignant gliomas.

OBJECTIVE: Animal and human studies have shown increased delivery of radiolabeled compounds across the blood-brain-tumor barrier using intra-arterial (IA) Cereport (RMP-7; Alkermes Inc., Cambridge, MA) with a radiolabeled tracer. This present study assesses the safety, tolerance, and preliminary efficacy of the IA administration of carboplatin with Cereport. METHODS: An open-label dose escalation study of IA Cereport (10-300 ng/kg) with 100 mg of IA carboplatin was conducted in 11 patients with recurrent malignant gliomas and 1 patient treated adjuvantly after radiation therapy. Tumor size and laboratory and clinical statuses were assessed. RESULTS: Adverse events were mainly neurological in nature and corresponded to the anatomic location of the tumor. Karnofsky performance scale scores did not decline, overall, for those patients who had tumor response. Tumor shrinkage was observed in three of six evaluable patients who received a dose of 300 ng/kg with durable responses of 60, 64, and 106+ weeks. CONCLUSION: Previous studies have demonstrated increased permeability in human gliomas using IA Cereport. This study demonstrates durable imaging responses using 100 mg of IA carboplatin in combination with Cereport. The drug combination in this patient population seems to be safe and acceptable, providing a novel means of antitumor dose intensification.

MR-guided procedures using contemporaneous imaging frameless stereotaxis in an open-configuration system.

Frameless MR-guided procedures have had limited application using conventional closed magnets, due largely to the technical difficulties involved. As a result of in-room MR image-monitoring capabilities, new open-design magnets now allow frameless stereotaxis using contemporaneous imaging to guide more invasive procedures. We evaluate our clinical experience with this new technique. An open-design 0.2 T magnet (Siemens OPEN) combined with an in-room monitor was used for 33 frameless MR-guided procedures (aspiration cytology, biopsy, and/or treatment) in a variety of locations in the head, neck, spine, brain, pelvis, and abdomen. Success of the procedure was based on the ability to accurately position the instrument in the target region to allow biopsy and/or treatment. The open-design magnet allowed the physician to directly access the patient for frameless stereotaxis as the procedure was performed. The in-room monitor provided contemporaneous imaging feedback during the procedure for successful placement of the instrument in the target region. Twenty-eight biopsy and five treatment procedures were performed. In all cases the technique resulted in successful placement of the instrument within the target tissue to complete the procedure. MR-guided procedures using contemporaneous imaging frameless stereotaxis are possible in an open-design magnet with in-room image monitoring and offer exciting possibilities for further development.

Simultaneous PET and MR imaging.

We have developed a prototype PET detector which is compatible with a clinical MRI system to provide simultaneous PET and MR imaging. This single-slice PET system consists of 48 2 x 2 x 10 mm3 LSO crystals in a 38 mm diameter ring configuration that can be placed inside the receiver coil of the MRI system, coupled to three multi-channel photomultipliers housed outside the main magnetic field via 4 m long and 2 mm diameter optical fibres. The PET system exhibits 2 mm spatial resolution, 41% energy resolution at 511 keV and 20 ns timing resolution. Simultaneous PET and MR phantom images were successfully acquired.

Intracarotid infusion of RMP-7, a bradykinin analog, and transport of gallium-68 ethylenediamine tetraacetic acid into human gliomas.

The bradykinin analog, RMP-7, was investigated for its ability to increase selectively the transport of 68Ga ethylenediamine tetraacetic acid (EDTA) into recurrent malignant gliomas in nine patients. For each patient, two position emission tomography (PET) studies (one with and one without RMP-7) were performed. For studies with RMP-7, 10 to 300 ng/kg of the compound was infused into the supraophthalmic carotid artery over 15 minutes. In each PET study, a sequence of PET scans was initiated simultaneously with an intravenous bolus of 68Ga EDTA (5-10 mCi). Arterial samples were taken to provide the input function. All PET scans were coregistered to the magnetic resonance (MR) images of the patient. Regions of interest were defined for tumor and normal tissue regions on MR images and were copied to the coregistered PET dynamic images to provide brain tissue-time activity curves. The constant (Ki) for the transport of gallium-68 from plasma to brain tissue was determined using a simple compartmental model. Intracarotid infusion of RMP-7 significantly increased transport into tumor regions with an average increase of 46 +/- 42% (mean +/- standard deviation, p < 0.05). Permeability in normal tissue regions was not significantly increased. Tumors in three of six patients treated with 300 ng/kg RMP-7 and carboplatin had at least a 50% reduction in tumor volume as measured by MR imaging. Intracarotid infusion of RMP-7 is a novel technique for selective delivery of antitumor compounds into brain tumors.

Biopsy of hepatic dome lesions: semi-real-time coronal MR guidance technique.

OBJECTIVE: MR imaging, with its coronal imaging capability, may be ideally suited for biopsies of hepatic dome lesions. We are reporting on the successful semi-real-time biopsy of such lesions using a 0.2-T open-configuration MR scanner in five patients. CONCLUSION: MR guidance holds promise for facilitating biopsies of hepatic dome masses.

Frequency-selective fat suppression MR imaging. Localized asymmetric failure of fat suppression mimicking orbital disease.

Our objectives were to further characterize an artifact related to the localized failure of the frequency-selective (FATSAT) fat suppression magnetic resonance (MR) imaging technique. We constructed two phantoms simulating human orbital anatomy and imaged them on a 1.5-T MR scanner using (FATSAT) and short T1 inversion recovery (STIR) techniques of fat suppression. The first phantom resembled orbit structural configurations; it was imaged in coronal and axial planes and in varying orientations with respect to the main magnetic field (Z axis) to study the features of the artifact and to reproduce the asymmetry seen in clinical cases. We designed the second phantom to enable quantification of the change in artifact size with change in orientation. We imaged the orbits of a normal human volunteer in similar planes and orientations, and compared the results to clinical cases demonstrating the artifact and true orbital disease. The artifact identified with localized failure of FATSAT fat suppression manifested as regions of hyperintensity maximal at fat-air interfaces, with gradual fading of the increased signal with distance from the interfaces. The artifact was most prominent when the interfaces were perpendicular to the axis of the main magnetic field (Z axis). The regions of increased brightness obscured normal orbital structures but were not associated with alterations in the geometry of these structures. Changes in orientation of the interfaces with respect to the Z axis, both in the phantoms and normal volunteer, reproduced the asymmetry of fat suppression failure seen in clinical cases. The relationship of size of the artifact to change in orientation was non-linear. The artifact was not seen on STIR images. We concluded that failure of FATSAT fat suppression may mimic orbital disease, particularly if asymmetric. As predicted by the Maxwell electromagnetism equation, slight variations in orientation of the fat-air interface to the Z axis may produce large asymmetries in fat suppression failure in the orbit. Confirmation may require either comparison with additional pulse sequences [T1-weighted spin echo (T1W SE) or STIR] or repositioning the patient's head to check for persistence of the finding with varying orientations.

MR-guided percutaneous ethanol ablation of liver tissue in a .2-T open MR system: preliminary study in porcine model.

The purpose of this study was to test the feasibility of MR-guided percutaneous ethanol ablation of liver tissue on a .2-T open MR scanner. Needles were placed by MR guidance first into an ex vivo sheep liver and then into livers of three anesthetized pigs, and injection of 10 ml of 96% alcohol was performed. T1 fast low-angle shot (FLASH), T2 turbo spin echo (TSE), and T1 spin echo (SE) images were obtained after incremental volumes of injection. In one pig, simultaneous injection of saline into normal liver was also performed with subsequent pathological correlation. Ethanol-infiltrated liver was hypointense to liver on all sequences, whereas saline caused no tissue signal changes on T1 SE and either isointense or hyperintense changes on T2 TSE images. Pathological examination confirmed ethanol-induced acute liver changes as compared with the control. MR guidance of needle placement and monitoring of ethanol effects on liver tissue is feasible. This may have implications for potential MR-guided hepatic tumor ablation.

Interventional magnetic resonance imaging of the head and neck and new imaging techniques.

The use of magnetic resonance imaging to directly guide therapy is a new area of investigation. Clinical magnetic resonance imaging has the potential to evolve from a purely diagnostic tool into a guide for invasive procedures. The idea of using magnetic resonance to guide percutaneous biopsy developed one decade ago. Magnetic resonance-guided fine-needle aspiration for head and neck lesions has become a standard technique some institutions. Once the needle reaches a lesion in the head and neck, it is natural to explore the possibility of treatment in the same setting. The concept of interventional magnetic resonance imaging has generated interest among radiologists, surgeons, and manufacturers. This article provides an overview of interventional procedures of the head and neck and other new imaging techniques that have been developed.

Magnetic resonance imaging of plantar plate rupture.

Degenerative plantar plate failure is an under-recognized cause of lesser metatarsalgia. We performed magnetic resonance imaging (MRI) with a small receiver coil in 13 patients in whom plantar plate ruptures of the second or third metatarsophalangeal joint were clinically suspected. In eight patients, MRI showed focal hyperintensity in the plantar plate that was interpreted as a rupture of the plate. Ruptures were confirmed in all five patients who underwent an operative procedure to treat the unstable, painful metatarsophalangeal joint. MRI is a noninvasive technique that can visualize plantar plate abnormalities and aid the clinical evaluation of problematic lesser metatarsalgia.