Salim Si-Mohamed
email: salim.si-mohamed@chu-lyon.fr

Sara Boccalini

Pierre-Antoine Rodesch

Riham Dessouky

Elias Lahoud

Thomas Broussaud

Monica Sigovan

Delphine Gamondes

Philippe Coulon

Yoad Yagil

Loïc Boussel

Philippe Douek

Affiliations

Feasibility of lung imaging with a large field-of-view spectral photon-counting CT system

Keywords: iDose, Lung, Phantoms, Photon-counting detector, Tomography, X-ray computed CT: computed tomography CTDIvol: volume CT dose index EID: energy-integrating detectors FOV: field-of-view HR: High-resolution HU: Hounsfield unit MTF: modulation transfer function PCD: photon-counting detector SPCCT: spectral photon-counting computed tomography

de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

During the past five years, a new generation of computed tomography (CT) devices equipped with energy-resolved photon-counting detectors (PCDs) has emerged with promising results for various pre-clinical and clinical applications [START_REF] Si-Mohamed | Review of an initial experience with an experimental spectral photon-counting computed tomography system[END_REF][START_REF] Si-Mohamed | Clinical perspectives of spectral photon-counting CT[END_REF][START_REF] Taguchi | Vision 20/20: single photon counting x-ray detectors in medical imaging[END_REF]. These initial studies have focused on imaging tasks that could benefit from high-resolution (HR) and lower radiation dose capabilities such as lung imaging [START_REF] Kopp | Evaluation of a preclinical photon-counting CT prototype for pulmonary imaging[END_REF][START_REF] Symons | Low-dose lung cancer screening with photon-counting CT: a feasibility study[END_REF][START_REF] Bartlett | High-resolution chest computed tomography imaging of the lungs: impact of 1024 matrix reconstruction and photon-counting detector computed tomography[END_REF].

Compared to energy integrating detectors (EIDs) used in conventional and dual-energy CT systems, PCD technology takes advantage of the absence of scintillators which require reflective layers between detector pixels [START_REF] Taguchi | Vision 20/20: single photon counting x-ray detectors in medical imaging[END_REF][START_REF] Blevis | X-Ray detectors for spectral photon-counting CT[END_REF]. This minimizes pixel size and maximizes spatial resolution. PCDs also use a direct conversion technology counting the photons incoming into detector pixels and sorting them into several energy bins. This suppresses electronic noise inside the readout circuit of each pixel by setting energy thresholds over the noise values (around 20-25 keV) [START_REF] Hsieh | Design considerations for photon-counting detectors: connecting detectors characteristics to system performances[END_REF]. Due to multiple energy bins, SPCCT systems can provide both conventional and material decomposition images as with dual-energy systems [START_REF] Si-Mohamed | Head-to-head comparison of lung perfusion with dual-energy CT and SPECT-CT[END_REF][START_REF] Jamali | Virtual unenhanced phase with spectral dual-energy CT: is it an alternative to conventional true unenhanced phase for abdominal tissues?[END_REF] but with the additional value of K-edge imaging of high atomic number materials, known as material specific quantitative imaging [START_REF] Si-Mohamed | Review of an initial experience with an experimental spectral photon-counting computed tomography system[END_REF][START_REF] Si-Mohamed | Evaluation of spectral photon counting computed tomography K-edge imaging for determination of gold nanoparticle biodistribution in vivo[END_REF][START_REF] Cormode | Multicolor spectral photon-counting computed tomography: in vivo dual contrast imaging with a high count rate scanner[END_REF][START_REF] Si-Mohamed | Multicolor imaging with SPCCT: an in vitro study[END_REF][START_REF] Si-Mohamed | Improved peritoneal cavity and abdominal organ imaging using a biphasic contrast agent protocol and spectral photon counting computed tomography K-edge imaging[END_REF][START_REF] Sigovan | Feasibility of improving vascular imaging in the presence of metallic stents using spectral photon counting CT and K-edge imaging[END_REF].

While EIDs only measure the amount of energy deposited in each pixel due to an indirect conversion that boosts the weight of high-energy photons, PCDs measure the photon counts per bin. The energy weighting of the lower energy photons is consequently more important in PCDs. This effect leads to higher tissue contrast since material attenuation depends on the energy with an increase in photoelectric attenuation coefficient towards the lower energy spectrum (~30-40 keV) [START_REF] Blevis | X-Ray detectors for spectral photon-counting CT[END_REF]. These technical features may explain why SPCCT technology holds the promise of being the next-generation of CT systems. Nevertheless, these systems still have limitations, such as field-of-view (FOV), detector array size, and count rates. In an attempt to overcome these current limitations, a large FOV SPCCT prototype has been built.

In the present study, the purpose was to characterize the technical capabilities and feasibility of a large FOV clinical SPCCT prototype in HR lung imaging.

Material & methods

SPCCT system

A large FOV (500 mm in-plane) clinical prototype system (Philips Healthcare) equipped with energy-sensitive PCDs of 2-mm-thick cadmium zinc telluride with a pixel pitch of 270 × 270 μm 2 at isocenter, bonded to Philips' proprietary ChromAIX2 applicationspecific integrated circuit, relying on the direct conversion high band gap semiconductor of cadmium zinc telluride was used for this study [START_REF] Steadman | ChromAIX2: a large area, high count-rate energyresolving photon counting ASIC for a spectral CT prototype[END_REF]. Each channel offered pulse-height discrimination with five controllable energy thresholds from 30 to 120 keV. The full spectral image chain followed a two-step approach for reconstruction. The photon counts from the five energy bins were used to provide conventional CT images. For each pixel, a maximum likelihood estimator was used to derive an equivalent water-thickness per pixel from the photon counts in the five energy bins. Conventional images were then reconstructed from the water-thickness equivalent sinograms using a filtered back-projection algorithm. A photograph of the system and schematic representation of the photon-counting measurement process is given in Figure 1. Further technical details are provided in Table 1.

Phantom experiments

Spatial resolution imaging

In order to assess the in-plane spatial resolution, a phantom with a 20 cm epoxy interior and solid water shell containing a 50 μm tungsten wire positioned 15 mm off the isocenter (slice sensitivity and geometric evaluation module, advanced iqModules TM , Gammex, Middleton, WI) was scanned in the axial mode at 120 kVp, 200 mAs. The resolution was evaluated quantitatively using the modulation transfer function (MTF). Conventional images, representing a region-of-interest around the wire were reconstructed with a 60 mm FOV, matrix size of 2048, and a slice thickness of 0.275 mm (voxel size at 0.029 (x) × 0.029 (y) × 0.275 (z) mm 3 ) using a PCD adapted high-resolution back-projection filter (filter Detailed 1).

The reconstructed images were analyzed using an in-house Matlab tool that produced the radial profile obtained from averaging several slices and derived the MTF curve by Fourier transform of the radial profile with compensation for the finite wire diameter. In addition, a subjective evaluation of a line pair phantom (high-contrast resolution module, advanced iqModules TM , Gammex), scanned in axial mode at 120 kVp, 200 mAs was performed. This module features line pairs with resolutions up to 32 lp/cm. The phantom was scanned in different positions so that each acquisition focused on 1 module of interest placed 15 mm off its isocenter. Conventional images were reconstructed with the same parameters previously described.

Lung nodule imaging

An anthropomorphic lung phantom (QRM-lung nodule phantom, GmbH) housing two types of spherical nodules (i.e., a subsolid one with mixed density [shell: -795 Hounsfield unit (HU), center: 50 HU at 120 kVp] and a second solid one [20 HU at 120 kVp]), was scanned using different radiation doses. The phantom had a water equivalent diameter of 21.3 cm, corresponding to a standard size patient chest. Helical acquisitions were performed with standard (120 kVp, 62 mAs), low (120 kVp, 11 mAs), and lowest possible scanner setting equivalent to an ultra-low-dose protocol (80 kVp, 3 mAs) with a 1.03 pitch value and 0.33 s rotation time. Images were reconstructed with a 300 mm FOV, a 1024 matrix size, and 0.250 mm slice thickness and an appropriate (Detailed 2) filter.

HR human lung imaging

HR lung images of a 60-year-old male with body mass index of 30 kg/m 2 were acquired under the authorization of the local ethics committee (protocol number: 2018-A02696-49). Standard (120 kVp, 63 mAs) and low-dose (120 kVp, 11 mAs) lung imaging was performed. This volunteer had undergone a previous standard dose (120 kVp, 103 mAs) high-resolution lung CT in our institute using a conventional CT system (Brilliance 64; Philips) that allowed for image quality comparison. Images were reconstructed with a 1024 matrix, a 300 mm FOV and a 0.25 mm slice thickness using filtered-back projection and two levels of hybrid iterative reconstruction algorithm (iDose level 5 and 9) adapted for photon-counting data. Acquisition and reconstruction parameters are summarized in Table 2.

A subjective comparison of image quality between conventional CT and SPCCT images reconstructed with a filtered-back projection algorithm was performed independently by three independent readers (DG, SB, SS-M with 15, 6 and 6 years of experience in lung imaging respectively) on a clinical workstation. Each reader rated the conspicuity and sharpness of different lung structures (distal airways, fissure, distal vessels, proximal bronchial wall), the subjective image noise using a 5-point Likert scale (1: unacceptable, 2: suboptimal, 3: acceptable, 4: above average, 5: excellent) and the overall image quality using a 4-point Likert scale (1: not evaluable, 2: interpretable despite moderate artefact or noise, 3: fully interpretable with mild artifacts or noise, 4: fully interpretable with no artifacts or noise).

Objective image noise was measured in a 40 mm 2 region-of-interest drawn in a peripheral aerated portion of the lung.

Radiation dose

Tube current, tube voltage and volumetric CT dose index (CTDIvol) were recorded. Due to a smaller z-axis collimation and consequent over-beaming (penumbra) compared to conventional CT, we found that the SPCCT prototype had a higher CTDIvol for the same tube voltage and current parameters. This consequent off-collimation radiation dose does not contribute to the image quality, but only to the CTDIvol. This means that a fair comparison between protocols has to be performed using the same acquisition parameters e.g. the X-ray flux (or total number of photons emitted by the X-ray tube) that is determined by mAs, kVp, system geometry, and tube filtration. Because of different X-ray filtration between the systems used in the present study, the flux of SPCCT was ~25% higher at same mAs than with conventional CT. Effective dose was estimated from the product of the dose length by the normalised effective dose conversion coefficient of 0.014 mSv.mGy -1 .cm -1 [START_REF] Bongartz | European guidelines on quality criteria for computed tomography[END_REF].

Statistical analysis

Image quality rating was averaged among the three readers and data were expressed as mean values.

Results

Phantom experiments

Spatial resolution imaging

Mean spatial resolutions were measured at 11.6 and 22.3 lp/cm at 50% and 10 % MTF respectively, with a cut-off at 31 lp/cm (Figure 2A). Visual evaluation of the line pair phantom allowed visualization of up to 28 lp/cm, corresponding to a line width of 178 µm (Figure 2B).

Lung nodule phantom imaging

The borders of both nodules as well as the ground glass portion of the subsolid nodule were well defined at 62 mAs (CTDIvol at 6.65 mGy) (Figure 3). With the low-dose protocol at 11 mAs (CTDIvol at 1.11 mGy), the margins appeared less defined but nodules were clearly depicted nonetheless. With the ultra-low-dose protocol at 80kVp and 3 mAs (CTDIvol at 0.10 mGy), the ground glass portion was more difficult to distinguish from background noise. In this case, the use of iDoses 5 and 9 improved border and ground glass opacity visualization (Figure 3). all readers agreed that the conspicuity and sharpness of the lung structures were preserved with the added benefit of noise reduction (Figure 4).

HR human lung imaging

Discussion

High-resolution CT imaging is necessary for various clinical applications in the lung such as parenchymal and interstitial tissue, distal airway and vessel assessment [START_REF] Hatabu | Interstitial lung abnormalities detected incidentally on CT: a Position Paper from the Fleischner Society[END_REF][START_REF] Lynch | Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society white paper[END_REF][START_REF] Bankier | Recommendations for measuring pulmonary nodules at CT: a statement from the Fleischner Society[END_REF][START_REF] Jalaber | Chest CT in COVID-19 pneumonia: a review of current knowledge[END_REF][START_REF] Neveu | Incidental diagnosis of Covid-19 pneumonia on chest computed tomography[END_REF][START_REF] Cao | Discriminating between bronchiolar adenoma, adenocarcinoma in situ and minimally invasive adenocarcinoma of the lung with CT[END_REF]. In this study, we showed the high-resolution capabilities of a large FOV SPCCT prototype suitable for these imaging tasks. We demonstrated that it is possible to visualize up to 28 lp/cm on a line pair phantom. Feasibility of solid and mixed nodules depiction has been shown under standard, low and ultra-low radiation doses. Finally, acquisitions on a human volunteer demonstrated high image quality compared to conventional CT even with lower radiation doses.

SPCCT technology represents a breakthrough in the medical computed tomography field because of the new PCDs. Their architectural features allows a much smaller pixel size (around 100-500 microns) than EIDs [START_REF] Taguchi | Vision 20/20: single photon counting x-ray detectors in medical imaging[END_REF][START_REF] Blevis | X-Ray detectors for spectral photon-counting CT[END_REF][START_REF] Hsieh | Design considerations for photon-counting detectors: connecting detectors characteristics to system performances[END_REF]. Furthermore, PCD manufacturers have decreased the area of each detector pixel to minimize the count rate per pixel, avoiding loss of photon counts and mis-registration of photon energy occurring at high count rates [START_REF] Taguchi | Vision 20/20: single photon counting x-ray detectors in medical imaging[END_REF][START_REF] Blevis | X-Ray detectors for spectral photon-counting CT[END_REF]. This is of great interest for spatial resolution capabilities. An additional feature of PCDs is the higher dose efficiency owing to electronic noise suppression. This is explained by the energyresolving characteristics that detect and measure electronic noise as photons of low-energy (around 20-25 keV). By fixing the lower threshold of detection at a value higher than this energy range (e.g., 30 keV on the current system), the electronic noise will not be recorded [START_REF] Taguchi | Vision 20/20: single photon counting x-ray detectors in medical imaging[END_REF][START_REF] Blevis | X-Ray detectors for spectral photon-counting CT[END_REF][START_REF] Hsieh | Design considerations for photon-counting detectors: connecting detectors characteristics to system performances[END_REF]. These key features explain the potential of SPCCT technology in HR lung imaging as highlighted in this study. First, MTF performance was reported 10 % at 22.3 lp/cm with a cutoff at 31 lp/cm. Evaluation of a line pair phantom depicted a 178 µm line width which is in line with photon-counting detector expectations [START_REF] Kopp | Evaluation of a preclinical photon-counting CT prototype for pulmonary imaging[END_REF][START_REF] Leng | 150-μm Spatial resolution using photon-counting detector computed tomography technology: technical performance and first patient images[END_REF][START_REF] Da Silva | Resolution characterization of a silicon-based, photon-counting computed tomography prototype capable of patient scanning[END_REF]. Despite the high performance and because of intrinsic limitations of MTF evaluation (e.g. high radiation dose with a highcontrast object), a subjective analysis remains mandatory using standard clinical protocols.

Second, in vitro lung nodule imaging demonstrated excellent image quality under standard radiation dose. This has been previously demonstrated with a limited FOV SPCCT from the same manufacturer [START_REF] Symons | Feasibility of dose-reduced chest CT with photon-counting detectors: initial results in humans[END_REF]. Third, image quality in a human volunteer scan showed a unanimous excellent overall image quality among three experienced lung radiologists. The image noise was excellent with a particular texture that characterizes high frequency noise, such as expected with PCDs [START_REF] Blevis | X-Ray detectors for spectral photon-counting CT[END_REF]. Small lung structures, i.e. distal airways and vessels, bronchial wall and fissures were also depicted with high quality, such as suggested previously using a limited FOV SPCCT from a different manufacturer [START_REF] Symons | Feasibility of dose-reduced chest CT with photon-counting detectors: initial results in humans[END_REF]. Finally, comparison between SPCCT and conventional CT images demonstrated a greater conspicuity and sharpness of various small lung structures and a greater overall image quality on SPCCT images among all subjective image readers, confirming the results from a recent study using a different limited FOV SPCCT system [START_REF] Bartlett | High-resolution chest computed tomography imaging of the lungs: impact of 1024 matrix reconstruction and photon-counting detector computed tomography[END_REF]. Furthermore, a greater subjective noise quality and similar noise values were found despite different acquisition (flux reduction of 23%) and reconstruction (1024 matrix, 0.25 mm slice thickness) parameters known to result in increased noise values.

Nevertheless, these reconstruction parameters were chosen to convey the intrinsic spatial resolution of PCDs.

Another feature highlighted in this study is dose efficiency. First, we have shown the feasibility of an ultra-low-dose lung imaging (80kVp, 3 mAs) for depiction of solid and mixed nodules while maintaining a matrix size at 1024 mm and a high frequency filter. Solid nodules were visible without any post-processing method, while mixed nodule quality was subjectively judged to be of diagnostic quality only in combination with an iterative reconstruction adapted for PCD, as is usually done for ultra-low-dose protocols [START_REF] Greffier | CT dose optimization for the detection of pulmonary arteriovenous malformation (PAVM): a phantom study[END_REF]. But for ULD protocols with conventional CT, lower frequency filter, matrix size of 512, slice thickness of 1.5 mm in addition to the use of denoising algorithms such as iterative reconstruction are recommended [START_REF] Greffier | CT dose optimization for the detection of pulmonary arteriovenous malformation (PAVM): a phantom study[END_REF][START_REF] Beregi | Low and ultra-low-dose radiation in CT: opportunities and limitations[END_REF][START_REF] Greffier | CT iterative reconstruction algorithms: a task-based image quality assessment[END_REF]. It is worth mentioning that conspicuity of ground glass abnormalities under ultra-low-dose conditions improved with use of higher levels of iterative reconstruction, suggesting both improvements in contrast and dose efficiency as well as spatial resolution for PCDs compared to EIDs [START_REF] Taguchi | Vision 20/20: single photon counting x-ray detectors in medical imaging[END_REF]. Furthermore, low-dose SPCCT imaging on a human volunteer showed acceptable noise quality despite a flux reduction of 89% compared to standard dose conventional CT imaging, a higher matrix size (1024) and a smaller slice thickness (0.25 mm). Nevertheless, SPCCT images demonstrated similar or greater conspicuity and sharpness of the lung structures. Finally, all readers found a similar overall image quality on low-dose SPCCT images compared to standard conventional CT images without the need for denoising algorithm. Combining these results demonstrates the capability to combine dose efficiency and high spatial resolution to acquire scans with lower radiation dose than with a conventional CT, such as suggested in initial studies [START_REF] Symons | Low-dose lung cancer screening with photon-counting CT: a feasibility study[END_REF][START_REF] Symons | Feasibility of dose-reduced chest CT with photon-counting detectors: initial results in humans[END_REF]. This also allows greater radiation dose optimization for other lung applications particularly ones associated with high cumulative dose in young patients with cystic fibrosis or pulmonary arteriovenous malformation [START_REF] Greffier | CT dose optimization for the detection of pulmonary arteriovenous malformation (PAVM): a phantom study[END_REF][START_REF] Fitton | Cumulative radiation dose after lung transplantation in patients with cystic fibrosis[END_REF].

In the field of high-resolution lung imaging, two commercial CT systems equipped with EIDs have proposed a high resolution mode with MTFs in the same range published with SPCCT (20-25 lp/cm at 50%) systems [START_REF] Oostveen | Physical evaluation of an ultra-high-resolution CT scanner[END_REF][START_REF] Kawashima | Technical note: performance comparison of ultra-high-resolution scan modes of two clinical computed tomography systems[END_REF]. However, these systems cannot offer the several advantages brought by PCDs such as the energy-resolved properties and radiation dose efficiency. This possibly explains the high radiation doses (volume CT dose index 13.65 mGy, mean dose-length product 588.3 mGy.cm) reported in a recent study for high-resolution imaging of lung adenocarcinoma [START_REF] Yanagawa | Lung adenocarcinoma at CT with 0.25-mm section thickness and a 2048 matrix: high-spatialresolution imaging for predicting invasiveness[END_REF].

The present study has limitations. First, an evaluation of the subjective and objective image quality is provided for one human volunteer. Second, no pathological lesions were found or characterized. Third, the volunteer did not represent the standard patient size limiting the applicability to standard lung imaging practice. Finally, exhaustive evaluation of image quality was out of the scope of the present study opening the way for further investigations.

In conclusion, a large FOV SPCCT prototype paves the way to a technology that not only can fulfil standard clinical requirements with high resolution and dose efficiency capabilities but also has the potential to overcome current CT limitations for lung imaging.

Figures captions

Figure 1. (A) Spectral photon-counting computed tomography prototype system. (B) Schematic representation of the photon-counting measurement process. Each individual X-ray interacting in the semi-conductor detector is creating electron-hole pairs. The number of pairs is directly proportional to the X-ray energy. High voltage applied to the electrodes allows collecting the charges in an electric pulse with intensity proportional to the X-ray energy. Multiple thresholds allow classifying each X-ray according to its energy.

Figure 5.

Human high-resolution spectral photon-counting computed tomography (SPCCT) lung imaging (high matrix, small slice thickness) as compared to a conventional CT scanner: focus on small bronchi (WL -600 HU, WW 1600 HU). Both columns show images of the lungs of the same human subject acquired with a Brilliance 64 CT system (first column) and with the SPCCT system (second column). First row shows a large FOV image of the chest. On the second row, small areas of equivalent dimensions of the right lung base are highlighted. A better definition of bronchial walls on the images obtained with the SPCCT is appreciated. On the third row, two even smaller portions of matching surface are pointed out. While on the Brilliance acquisition only background noise can be seen surrounding the bronchus in the centre, the SPCCT image shows a discontinuity of the bronchus corresponding to the origin of a 0.5 mm diameter bronchiole. Furthermore, the thin walls of the bronchiole can be appreciated as it winds away. Reconstruction parameters: Brilliance 64 -matrix 512; slice thickness, 0.800 mm; kernel, YA. SPCCT -matrix, 1024; slice thickness, 0.250 mm; filter, Detailed 2.

Table 1. System parameters of the clinical prototype spectral photon counting computed tomography (SPCCT) system.

Table 2. Acquisition and reconstruction parameters for conventional and spectral photoncounting computed tomography (SPCCT) imaging.

Table 3. Subjective image analysis of conventional and spectral photon-counting computed tomography (SPCCT) human lung imaging.

Figure 2 .

 2 Figure 2. Spectral photon-counting computed tomography key features imaging of spatial resolution. (A) Average modulation transfer functions across slices for the 50 μm tungsten wire scanned at 15 mm from isocenter (reconstruction parameters: 2048 matrix size, 60 mm field of view, filter Detailed 1, 0.275 mm slice thickness). (B) Images with a voxel size at 0.029 (x) × 0.029 (y) × 1.1 (z) mm 3 of high-contrast resolution module focused on visualization of 5 dense lines. Detectability of line pairs is possible up to 28 lp/cm (corresponding to a line thickness at 178 µm).

Figure

  Figure3. High matrix spectral photon-counting computed tomography (SPCCT) standard, low and ultra-low-dose imaging of lung nodules. Imaging characteristics of different nodules scanned with the SPCCT system (WL, -600 HU, WW, 1600 HU). Images were acquired with different radiation dose (ultra-low-dose, low-dose, standard dose) and reconstructed with filtered-back projection (FBP) and iterative reconstruction (iDose 5 and 9 for ultra-low-dose imaging). Reconstruction parameters: First and second row: First column: FOV, 300 mm; matrix, 1024; SW, 1 mm; filter, Detailed 2; FBP. Second column: FOV, 300 mm; matrix, 1024; SW, 0.250 mm; filter, Detailed 2; FBP. Third column: FOV, 300 mm; matrix, 1024; SW, 0.250 mm; filter, Detailed 2; FBP. Third row: FOV, 300 mm; matrix, 1024; SW, 1 mm; filter, Detailed 2; FBP; iDose, level 5 and 9.

Table 3

 3 Despite a tube flux reduction of 87% between low-dose SPCCT and standard dose conventional CT images, overall image quality was equivalent among both images (mean score of 3). Image noise was greater on low-dose SPCCT images compared to standard dose conventional CT images (142.7 HU vs. 82.5 HU), but subjective image quality remained acceptable (mean score of 3). The addition of iDose to SPCCT images decreased noise values by about 35% with iDose 5 and 68% with iDose 9 and changed the noise texture as expected from iterative reconstruction. Image quality was not rated, but

shows the subjective image quality analysis of HR lung imaging on conventional and SPCCT systems (Figures

4 and 5

). Conspicuity and sharpness of distal airways, fissures, distal vessels and proximal bronchial wall were greater on standard dose SPCCT images (mean score of 4 or 5). Despite a tube flux reduction of 23% for standard dose SPCCT images, overall image quality was greater on SPCCT images (mean score of 4 vs. 3) compared to conventional CT images. Despite higher matrix size and lower slice thickness of standard dose SPCCT images, noise values were equivalent (83.2 HU vs. 82.5 HU respectively), while subjective noise quality was greater (mean score of 5 vs 3.7 respectively) than conventional CT images. Conspicuity and sharpness of distal airways, fissures, distal vessels and proximal bronchial wall were either similar or greater on low-dose SPCCT images, (mean score of 3 or 4).

  3.High matrix spectral photon-counting computed tomography (SPCCT) standard, low and ultra-low-dose imaging of lung nodules. Imaging characteristics of different nodules scanned with the SPCCT system (WL, -600 HU, WW, 1600 HU). Images were acquired with These structures are better depicted on the SPCCT acquisition at 66 mAs (B1) compared to a conventional CT image (A) notwithstanding the higher dose of the latter. The fissures are also visible on the low-dose SPCCT acquisition (C) even if the background noise is increased. Note that the SPCCT images are at significantly narrower slice thickness: 0.250 mm as opposed to 0.800 mm in the Brilliance 64 CT image. B1-B3 show the same image obtained with SPCCT (120kVp and 66 mAs) and reconstructed with filtered back projection (B1), iDose level 5 (B2) and iDose level 9 (B3). C1-C3 show the same image obtained with low-dose SPCCT (120kVp and 11 mAs) and reconstructed with filtered back projection (C1), iDose level 5 (C2) and iDose level 9 (C3). Noise values were measured for each acquisition within the regions-of-interest shown in green in the images. Reconstruction parameters: Amatrix, 512; slice thickness, 0.800 mm; kernel YA. B1-B3 and C -matrix, 1024; slice thickness, 0.250 mm; filter, Detailed 2.

	Figure 4. Human high-resolution spectral photon-counting computed tomography (SPCCT) lung
	imaging (high matrix, small slice width) as compared to a conventional CT: low-dose and
	iterative reconstructions (WL -600 HU, WW 1600 HU). The small fissure (arrows) and an
	accessory fissure of the right inferior lobe (arrowheads) are shown on three acquisitions of the
	same subject obtained with a Brilliance ® 64 CT system (A, 120 kVp; 103 mAs; CTDIvol: 6.1 mGy;
	equivalent dose: 1.87 mSv) and with the SPCCT system (B and C) at standard (B, 120 kVp; 66
	mAs; CTDIvol: 6.65 mGy; equivalent dose: 2.00 mSv) and low-dose (C, 120kVp; 11 mAs; CTDIvol:
	1.11 mGy; equivalent dose: 0.33 mSv), respectively.

different radiation dose (ultra-low-dose, low-dose, standard dose) and reconstructed with filtered-back projection (FBP) and iterative reconstruction (iDose 5 and 9 for ultra-low-dose imaging). Reconstruction parameters: First and second row: First column: FOV, 300 mm; matrix, 1024; SW, 1 mm; filter, Detailed 2; FBP. Second column: FOV, 300 mm; matrix, 1024; SW, 0.250 mm; filter, Detailed 2; FBP. Third column: FOV, 300 mm; matrix, 1024; SW, 0.250 mm; filter, Detailed 2; FBP. Third row: FOV, 300 mm; matrix, 1024; SW, 1 mm; filter, Detailed 2; FBP; iDose, level 5 and 9.

Funding

This work was supported by European Union Horizon 2020 grant No 643694 and FLI imaging.

Human rights

The authors declare that the work described has been carried out in accordance with the Declaration of Helsinki of the World Medical Association revised in 2013 for experiments involving humans. The local ethics committee approved the study protocol (protocol number: 2018-A02696-49).

Informed consent and volunteer details

The authors declare that this report does not contain any personal information that could lead to the identification of the volunteer.

Disclosure of interest

Yoad Yagil, Philippe Coulon and Elias Lahoud are employees of Philips Healthcare, the manufacturer of the scanner. The other authors have no competing interest. 3 Data are expressed as mean score of the three different readers scores. Overall image quality was rated using a 4-points Likert scale (1: not evaluable, 4: fully interpretable with no artifacts or noise). Noise and lung structures image quality were rated using a 5-points Likert scale (1: unacceptable, 5: excellent). SPCCT = spectral photon-counting computed tomography

Author contributions


Christine Moroni
email: christine.moroni@univ-lille.fr

Catherine Belin
email: catherine.belin@aphp.fr

Contribution of the neuropsychological assessment in concussion

Keywords: Concussion, Neuropsychology, Cognitive assessment, Behavioral assessment Commotion cérébrale, Neuropsychologie, Evaluation cognitive, Evaluation comportementale

diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

impaired by concussion: attention, memory, visuospatial functions and executive functions. These abilities could be explored with "paper and pencil" tests or with computerized test batteries. While cognitive sequelae in the context of a moderate or a severe traumatic brain injury are consolidated, in the context of concussion, neuropsychological sequelae tend to resolve in a short tiime. As a consequence, several neuropsychological assessments could be conducting in a short period involving some methodological considerations. Moreover, as concussion could be reported in a Whiplash injury from a car crash with forensic consequences, it is crucial to propose tests to be sure that the weak performance obtained into the neuropsychological assessment is not explained by poor effort and/or malingering.

Discussion / Conclusion : This article revises these aspects of a neuropsychological assessment in the specific context of concussion.

Résumé

La réalisation d'une évaluation neuropsychologique est une étape indispensable dans la prise en charge des personnes victimes de commotions cérébrales ou de traumatismes crâniens légers.

Objectif : Présenter les différentes étapes d'une évaluation neuropsychologique exhaustive qui a pour but d'explorer la sphère comportementale ainsi que la sphère cognitive Méthode : Description de l'intérêt des principaux tests disponibles pour l'évaluation comportementale et cognitive. Le choix des tests reposent sur l'expérience clinique et l'expertise des auteurs.

Résultats :

Les séquelles comportementales (telle que la dépression, l'anxiété ou encore la fatigue) ainsi que leur

Introduction

Before the 1980s, most brain injury research focused on severe or moderate traumatic brain injury allowing one to describe a now well-known pattern of cognitive and neurological consequences of this kind of brain injury. In contrast, neurological and neuropsychological changes following mild traumatic injury or concussion (commonly used interchangeably [START_REF] Mullally | Concussion[END_REF]) were regarded as minor and inconsequential [START_REF] Johnson | Neuropsychological assessment of sport-related concussion[END_REF], whereas concussions involve a combination of physical (headache, dizziness…), cognitive and behavioral symptoms [START_REF] Rosenbaum | Neuropsychological assessment of sports-related concussion measuring clinically significant change[END_REF] provoking sometimes a complaint from patients. The neuropsychological assessment of the cognitive and behavioral symptoms from a concussion could be indispensable in certain contexts. For example, in a context of a rear-end car accidents (inducing a Whiplash injury), legal actions could be undertaken and litigation could involve the presence of cognitive impairment [START_REF] Vickery | Detection of inadequate effort on neuropsychological testing: a meta-analytic review of selected procedures[END_REF]. In a military context (blast injury), as in a sports context (amatory or professional contact sports, i.e. soccer, American football, ice hockey, rugby …), the assessment of cognitive and behavioral sequelae from concussion could be determinant to detect impairments that would hinder a successful return to daily life or to sport. Although, these sequelae are often brief, they tend to resolve within 7-10 days in a sport-related concussion, or after 2 or 3 months in the context of a whiplash [START_REF] Kessels | Cognitive functioning after whiplash injury: a meta-analysis[END_REF]. In a number of patients, the complaints still exist six months after the accident, resulting in a fairly high disability rate [START_REF] Spitzer | Scientific mono-graph of the Quebec Task Force on Whiplash-Associated Disorders: Redefining "whiplash" and its management[END_REF]. Accordingly, in front of any cognitive and/or behavioral complaint after concussion, a neuropsychological assessment has to be proposed. Moreover, as there is a consensus in the literature [START_REF] Mittenberg | Mild traumatic brain injury and post-concussion syndrome[END_REF] indicating that persistent symptoms from a concussion are related to anxiety and stress rather than cognitive impairment, the recommended neuropsychological assessment needs to include a battery of tests designed to assess a wide range of domains, with the aim of providing specific information regarding behavioral and cognitive status [START_REF] Merritt | Normative Data for a Comprehensive Neuropsychological Test Battery used in the Assessment of Sports-Related Concussion[END_REF].

Method

The objective of this article is to propose a comprehensive overview and description of the value of the main tests available for behavioral and cognitive assessment. As this is neither a meta-analysis nor an extensive review of all previously published papers, the choice of tests is based on the clinical experience and expertise of the authors. This work aims to highlight the tests that appear to be the most suitable and reliable in their design and practicality to explore the different cognitive and behavioral effects of concussions.

Results

Behavioral Assessment

The behavioral semiology combines mood lability, irritability, insomnia, anxiety and depression with, sometimes, some personality changes [START_REF] Mullally | Concussion[END_REF]. None of these signs are specific or pathognomonic. To catch these symptoms as their impact in daily life, the neuropsychological assessment shall include the Rivermead Post-Concussion Symptoms Questionnaire [START_REF] King | The Rivermead post concussion symptoms questionnaire: a measure of symptoms commonly experienced after head injury and its reliability[END_REF] or the Profil of Mood Stats (POMS) [START_REF] Mcnair | Manual for the Profile of 14 Mood States[END_REF], and also questionnaires to apprehend depressive symptoms (BDI -II, [START_REF] Beck | Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients[END_REF]), anxiety symptoms (STAI, [START_REF] Spielberger | State-Trait Anxiety Inventory and State-Trait Anger Expression Inventory[END_REF]) and fatigue (Multidimensional Fatigue Inventory, MFI -20 [START_REF] Gentile | Validation of the French "multidimensional fatigue inventory" (MFI 20)[END_REF][START_REF] Manoli | Is Multidimensional Fatigue Inventory (MFI-20) adequate to measure brain injury related fatigue?[END_REF]).

The Rivermead Post-Concussion Symptoms Questionnaire [START_REF] King | The Rivermead post concussion symptoms questionnaire: a measure of symptoms commonly experienced after head injury and its reliability[END_REF] is the questionnaire the most commonly used; it can be self-administered or given by an interviewer. Participants are asked to rate how severe each of the 16 symptoms has been over the past 24 hours. In each case, the symptom is compared with how severe it was before the injury occurred. The 16 symptoms are: headaches, dizziness, nausea, hyperacusis (or noise sensitivity), sleep disturbance, fatigue, irritability, feeling depressed, feeling frustrated, poor memory, poor concentration, taking longer to think, blurred vision, light sensitivity, double vision and restlessness.

The POMS [START_REF] Mcnair | Manual for the Profile of 14 Mood States[END_REF] exists in several versions. The most commonly used is the POMS 2, which is available for adults aged 18 years and older and is available as full-length (65 items) or short versions (35 items). This questionnaire contains a series of descriptive words/statements that describe feelings people have. Subjects self-report on each of these areas using a 5-point Likert scale.

The BDI-II [START_REF] Beck | Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients[END_REF], STAI [START_REF] Spielberger | State-Trait Anxiety Inventory and State-Trait Anger Expression Inventory[END_REF] and MFI-20 [START_REF] Gentile | Validation of the French "multidimensional fatigue inventory" (MFI 20)[END_REF][START_REF] Manoli | Is Multidimensional Fatigue Inventory (MFI-20) adequate to measure brain injury related fatigue?[END_REF] are specific to a behavioral sphere and less focused on the functional impact. The BDI -II [START_REF] Beck | Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients[END_REF] is a 21-question multiple-choice selfreport inventory, one of the most widely used psychometric tests for measuring the severity of depression. Each answer is scored on a scale value of 0 to 3. Higher total scores indicate more severe depressive symptoms. The standardized cutoffs are: 0-13 minimal depression, 14-19 mild depression, 20-28 moderate depression and a score higher to 29 severe depression.

The STAI [START_REF] Spielberger | State-Trait Anxiety Inventory and State-Trait Anger Expression Inventory[END_REF] is a psychological inventory based on a 4-point Likert scale and consists of 40 questions on a self-report basis. It measures two types of anxiety -state anxiety (or anxiety about an event), and trait anxiety (or anxiety level as a personal characteristic). The multidimensional fatigue inventory (MFI-20) [START_REF] Gentile | Validation of the French "multidimensional fatigue inventory" (MFI 20)[END_REF][START_REF] Manoli | Is Multidimensional Fatigue Inventory (MFI-20) adequate to measure brain injury related fatigue?[END_REF] is a self-assessment instrument with 20 items including five dimensions of fatigue: General fatigue, Physical fatigue, two scales covering reduction in activities and lack of motivation to start an activity (Reduced activities and Reduced motivation) and Cognitive fatigue.

Cognitive Assessment

The cognitive semiology of a concussion is characterized at first by a mental fogginess, the patient experiences a subjective sensation of mental clouding described as feeling "foggy" and highlighted by poor performance on diverse tasks, in various degrees, and affecting different cognitive fields [START_REF] Kessels | Cognitive functioning after whiplash injury: a meta-analysis[END_REF]. Main cognitive sequelae from a concussion concern four cognitive spheres: attention, memory, visuospatial functions and executive functions [START_REF] Beeckmans | Persistent cognitive deficits after whiplash injury: a comparative study with mild traumatic brain injury patients and healthy volunteers[END_REF]. The integrated operation of these spheres could be explored as well as with "paper and pencil" tests or with computerized test batteries.

The "paper and pencil" tests usually applied in the cognitive assessment design to evaluate the consequences of a concussion are those used to assess cognitive deficit after a mild or a severe brain injury. To assess attention, the Paced auditory serial addition test (PASAT) [START_REF] Gronwall | Memory and information processing capacity after closed head injury[END_REF], D-2 test [START_REF] Ross | Normative data for the d2 Test of attention: an examination of age, gender, and cross-cultural Indices[END_REF], the Symbol Digit Modalities Test (SDMT) [START_REF] Smith | Symbol Digit Modalities Test (SDMT). Manual (Revised)[END_REF] are commonly used.

The PASAT [START_REF] Gronwall | Memory and information processing capacity after closed head injury[END_REF] is used to assess sustained and divided attention. It is a very challenging task that involves working memory, auditory information processing speed, flexibility and calculation abilities. In this task, patients are given a number every 3 seconds and are asked to add the number they just heard to the number they heard just before.

The D2 test [START_REF] Ross | Normative data for the d2 Test of attention: an examination of age, gender, and cross-cultural Indices[END_REF] is also used to assess selective and sustained attention and involves as well visual scanning speed. This test asks participants to cross out any letter d with two marks around above it or below it in any order. The surrounding distractors are usually similar to the target stimulus, for example a p with two marks or a d with one or three marks.

The SDMT [START_REF] Smith | Symbol Digit Modalities Test (SDMT). Manual (Revised)[END_REF] is a brief test which involves a simple substitution task. Using a reference key, the examinee has 90 seconds to pair specific numbers with given geometric figures. This task involves only geometric figures and numbers, the SDMT is relatively culture free as well, and can also be administered to illiterate individuals.

To assess memory, one could choose the Digit Span [START_REF] Baddeley | Short-term memory for word sequences as a function of acoustic, semantic and formal similarity[END_REF] (forward and backward) for shortterm memory and the Rey auditory verbal learning test [START_REF] Schoenberg | Test performance and classification statistics for the Rey Auditory Verbal Learning Test in selected clinical samples[END_REF], the Hopkins Verbal learning test [START_REF] Brandt | The Hopkins verbal learning test: Development of a new memory test with six equivalent forms[END_REF], or the California Verbal learning Test (CVLT) [START_REF] Delis | CVLT, California Verbal Learning Test: Adult Version: Manual[END_REF] for the verbal episodic aspects of long-term memory (semantic and procedural memories are usually not altered in the context of concussion). The digit span test [START_REF] Baddeley | Short-term memory for word sequences as a function of acoustic, semantic and formal similarity[END_REF] is a measure of the working memory. Working memory is a cognitive system with a limited capacity that is responsible for temporarily holding information available for a processing (as a calculation). This ability is important for reasoning and the guidance of decision-making. Working memory is often used synonymously with the term: short term memory. This digit span task determines the longest list of items that a person can repeat back in a correct order (forward or backward according to the instruction) immediately after presentation. It is a common measure of short-term memory and refers to the ability of an individual to reproduce immediately, after one presentation, a series of discrete stimuli. The Rey auditory verbal learning test [START_REF] Schoenberg | Test performance and classification statistics for the Rey Auditory Verbal Learning Test in selected clinical samples[END_REF], the Hopkins Verbal learning test [START_REF] Brandt | The Hopkins verbal learning test: Development of a new memory test with six equivalent forms[END_REF] and the California Verbal Learning Test [START_REF] Delis | CVLT, California Verbal Learning Test: Adult Version: Manual[END_REF] are three tests assessing verbal long-term memory based on the recall of a list of words. In the California Verbal Learning Test, these words share semantic links. These three tests allow clinicians to assess processing of encoding, storage and restitution of information in verbal long-term memory.

To assess the visuospatial function, the most frequently mentioned "paper and pencil" tests are the Hooper visual organization test [START_REF] Tamkin | Age-related norms for the Hooper Visual Organization Test[END_REF] and the Benton judgement of line orientation test [START_REF] Calamia | Developing a short form of Benton's judgment of line orientation test: An item response theory approach[END_REF]. The Hooper Visual Organization Test is known to be a measure of visual integration whereas the Benton judgement of line orientation test was developed to be a measure of visual reasoning and visuo-constructive abilities.

The executive functions are apprehended with the Trail Making Test (A and B) [START_REF] Roussel | La batterie GREFEX : données normatives[END_REF] which tests mental flexibility and shifting abilities, the Stroop test [START_REF] Roussel | La batterie GREFEX : données normatives[END_REF] which involved inhibitory processing and the Controlled Oral Word Association Test (COWAT) [START_REF] Loonstra | COWAT metanorms across age, education, and gender[END_REF], a test of verbal fluency [START_REF] Vickery | Detection of inadequate effort on neuropsychological testing: a meta-analytic review of selected procedures[END_REF][START_REF] Kessels | Cognitive functioning after whiplash injury: a meta-analysis[END_REF][START_REF] Beeckmans | Persistent cognitive deficits after whiplash injury: a comparative study with mild traumatic brain injury patients and healthy volunteers[END_REF].

More recently, some computerized neuropsychological batteries have been developed to assess these four cognitive spheres. The best-known computerized battery to assess attention was proposed by Zimmermann and Fimm [START_REF] Zimmermann | Tests d'évaluation de l'attention (TEA)[END_REF]. In sport-related concussion, several computerized batteries have been developed such as the Automated Neuropsychological Assessment Metrics (ANAM) [START_REF] Levinson | Monitoring recovery from traumatic brain injury using automated neuropsychological assessment metrics (ANAM V1.0)[END_REF], CogState [START_REF] Maruff | Validity of the CogState brief battery: Relationship to standardized tests and sensitivity to cognitive impairment in mild traumatic brain injury, schizophrenia, and AIDS dementia complex[END_REF], Headminder Concussion Resolution Index [START_REF] Erlanger | Concussion Resolution Index™[END_REF] or ImPACT (Immediate Post-Concussion Cognitive Assessment and Testing) [START_REF] Schatz | Sensitivity and specificity of the ImPACT Test Battery for concussion in athletes[END_REF].

These computerized batteries, assessing the four cognitive spheres affected by a concussion, were developed for English native speakers.

Computerized neuropsychological assessments seem to be more sensitives to subtleties of recovery, notably because they are based on the analyze of reaction time measures. However, Randolph et al. [START_REF] Randolph | Is neuropsychological testing useful in the management of sport-related concussion?[END_REF] highlighted some methodological weakness of the computerized batteries. According to these authors, no or very few peer-reviewed papers have studied computerized batteries, their psychometric properties such as their reliability and validity.

Test reliability refers to the degree to which a test is consistent and stable in measuring what it is intended to measure. Test validity refers to the degree to which the test actually measures what it claims to measure and the extent to which inferences, conclusions and decisions made on the basis of test scores are appropriate and meaningful. Hence, before carrying out routinely these computerized batteries, some additional studies are needed and even more since some studies demonstrated the importance to use appropriate normative data in the assessment of sport-related concussion [START_REF] Merritt | Normative Data for a Comprehensive Neuropsychological Test Battery used in the Assessment of Sports-Related Concussion[END_REF]. Indeed, the use of normative data is a hallmark of the neuropsychological assessment process to be able to identify changes in cognitive functioning after a concussion and to attribute these changes to head injury. However, it could not be always adapted to use currently available normative data of tests. The normative data are established from a large panel of participants aged from 19 to 89-years-old with variants in their level of academic education. Appropriate normative data are needed because athletes or soldiers are generally young, some of them could have a history of a previous head injury or learning disorders or even hyperactivity disorders [START_REF] Merritt | Normative Data for a Comprehensive Neuropsychological Test Battery used in the Assessment of Sports-Related Concussion[END_REF].

Supplementary Assessment

In the specific context of a Whiplash injury from a car crash, there is at least one supplementary test to carry out during the neuropsychological assessment. Indeed, in this context, legal actions could be undertaken with the aim of identifying a handicap based on cognitive or behavioral sequelae [START_REF] Vickery | Detection of inadequate effort on neuropsychological testing: a meta-analytic review of selected procedures[END_REF]. The detection of poor effort and/or malingering shall be crucial in clinical neuropsychological practice in order to make accurate diagnoses, prognoses, and referrals. The criteria proposed by Slick, Sherman, and Iverson [START_REF] Slick | Diagnostic criteria for malingered neurocognitive dysfunction: proposed standards for clinical practice and research[END_REF] for Malingering Neurocognitive Dysfunction (MND) described in Table 1 constitute an interesting reference to guide the neuropsychologist to appreciate if a patient's performance during an evaluation is or is not really associated to his pathological condition (e.g. neurological, psychiatric). Some neuropsychological tests could be carried out in support of these criteria, such as, in the field of memory, the 15-items Rey [START_REF] Arnet | Quantitative and qualitative performance on Rey's 15-Item Test in neurological patients and dissimulators[END_REF], the test of Memory Malingering (TOMM) [START_REF] Tombaugh | The Test of Memory Malingering (TOMM): Normative data from cognitively intact and cognitively impaired individuals[END_REF], Amsterdam Short-Term Memory Test (ASTMT) [START_REF] Schagen | Amsterdam short-term memory test: a new procedure for the detection of feigned memory deficits[END_REF] or the 21-items Test [START_REF] Iverson | Application of a forced-choice memory procedure designed to detect experimental malingering[END_REF]. These tests are based on two conditions -free recall and -recognition. The usual patterns of responses of malingering patients is characterized by inconsistent errors in the recognition tasks with a normal free recall of the same items which is counterintuitive and the very opposite to amnesic patients' pattern of memory performance.

________________________________Insert here Table 1____________________________

Discussion / Conclusion

Neuropsychological examination is the established method of assessing cognitive and emotional status following a concussion. According to Moser et al. [START_REF] Moser | Neuropsychological evaluation in[END_REF], neuropsychologists possess the background knowledge and training to understand brain-behavior relationship. A neuropsychological assessment is indispensable during the subacute period of recovery following a concussion. Although the use of multiple task computerized battery seems to be attractive, it remains more prudent to use a computerized single task developed for a specific purpose, such as the measure of reaction time in the aim to study proceeding speed.

To achieve its objectives, a neuropsychological assessment needs time to be completed successfully namely exploring behavior and cognition without forgetting a possible exaggeration of symptoms. According to the concussion context (car accident, falls, sport and so on) to objective behavioral and cognitive sequelae is important in the management of the patients and to guide them towards a return to work or to a sport practice in a safe way. To ensure a correct return to a daily life, some psychological therapy based on cognitivebehavioral therapy or on neuropsychological therapy could be proposed.

Table 1 .

 1 the diagnosis and management of sports-related concussion. Arch Clin Neuropsychol 2007; 22: 909-16. https://doi.org/10.1016/j.acn.2007.09.004 Summary of the of Slick et al. (1999) criteria for Malingered Neurocognitive Dysfunction A. Presence of substantial external incentive B. Evidence from neuropsychological testing 1. Definite negative response bias 2. Probable response bias 3. Discrepancy between test data and known patterns of brain functioning 4. Discrepancy between test data and observed behavior 5. Discrepancy between test data and reliable collateral reports 6. Discrepancy between test data and documented background history C. Evidence from self-report 1. Self-reported history is discrepant with documented history 2. Self-reported symptoms are discrepant with known patterns of brain functioning 3. Self-reported symptoms are discrepant with behavioral observations 4. Self-reported symptoms are discrepant with information obtained from collateral informants 5. Evidence from exaggerated or fabricated psychological dysfunction D. Behaviors meeting necessary criteria from groups B and C are not fully accounted for by psychiatric, neurological, or developmental factors

	Definite

Meets criterion A AND criterion B1 AND criterion D. Probable Meets criterion A AND two or more B criteria (excluding B1); or, meets one B criterion (excluding B1) AND one or more C criteria. Possible Meets criterion A AND one or more C Criteria but NOT Criterion D; or, meets all criteria for Definite or Probable but DOES NOT meet criterion D