IMAGING FOR SCIENCE

PC PET/CT
in vivo molecular and preclinical imager

The first sub-half mm3 PET volumetric resolution PET/CT with

exceptional image quantification - accuracy over 97 %

Preclinical Line
 PET/CT Introduction
To unveil fine and accurate details of living organisms, scientists need high resolution, high-sensitivity, time-dependent
quantitation. Definition of kinetic constants of biological processes also became a basic scientific aim.

Offering solutions for modern-day science, Molecular Imaging has gone a long way in a relatively short time to become
an indispensable tool for virtually any biologist. One of the most established methods in the field, Positron Emission
Tomography (PET) remains the cutting edge and it is still the gold standard in Molecular Imaging.

The reasons of this long-lasting premier position are robust quantitation, high time resolution and real three-
dimensional results combined with an adequate observational time window. With PET, fast and easy translation of a
result from the laboratory bench to its application in the clinic is also imminent.

In the last years almost every PET imaging result is supported by information about anatomical structures of live animals
through X-ray Computed Tomography (CT) imaging.

In the recent past Mediso developed innovative technologies that provided new perspectives to small animal imaging.
Now, the new nanoScan® PET/CT system offers user-friendly imaging and a large scope of applications in one simple to
use, high resolution, high-end PET/CT system. nanoScan® PET/CT is equipped with an imaging technology widely
considered as the most advanced PET and CT detector construction, data processing and reconstruciton chain in the
industry.

Main advantages of the system

- Highest PET resolution ever (using the industry's

most advanced pixelated modular LYSO detectors)

- State-of-the-art Tera-TomoTM 3D PET image

reconstruction engine

- Extremely fast, parallel workflow of data acquisition,

image reconstruction and image quantitation

- Uniquely easy access to the animal from

both the front and the back of the PET/CT gantry

- High imaging throughput by large bore size and large

field-of-view in both axial and transaxial directions

- No trade-off between resolution and sensitivity: high

resolution images are reconstructed from large
field-of-view, high-sensitvity data acquisitions

- High resolution and very low dose cone-beam CT imaging

- One-click MultiCellTM animal anesthesia / imaging bed

- Simple to use with reliable detector technology,

no need for long calibrations

Pursuit of perfection
Always eager to find an even better solution, Mediso constantly strives to develop the highest
level imaging technology possible.

We wish to serve the scientific community with our core value: supreme image quality.
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Relying on proven excellence

The gold standard of Molecular Imaging using Mediso's PET/CT technology

Animal imaging studies are performed to provide reliable quantitative results. Moreover, those studies often demand a
low limit of detection with high sensitivity. As imaging modality, PET will remain the gold standard of quantitation in
biology. This is due to PET's proven measurement accuracy throughout several orders of magnitude and exceptional,
unparalelled biological sensitivity inherent in isotopic tracing. PET's leadership in quantitation and sensitivity is
established by robust data. nanoScan® PET/CT ensures reaching the best imaging resolution with the highest sensitivity
in the whole body of the animal.

Mediso's unique PET detector technology enables you to detect femtomolar quantities of
proteins per milligram of tissue with high resolution and exquisite in vivo image quality.

MRI nanoScan® - the in vivo multimodality molecular imaging platform

Mediso nanoScan® family of imaging systems represents the microscopy level of in vivo
SPECT PET functional molecular imaging, nanoScan® is a continuous upgrade path to provide a total
solution with four high-power modalities: PET / SPECT / MRI / CT. The common MultiCellTM
animal imaging bed system, common precision gantry mechanics and software tools ensure
CT
that as your research grows, all your needs will be served by a Mediso product.

Continuous upgrade path for the existing NanoSPECT/CT ® users:

®
For imaging facilities already using the world market leader NanoSPECT/CT system (that has been also developed and
manufactured by Mediso) the nanoScan® PET/CT and the nanoScan® PET/MRI are unique opportunities to upgrade
onto the next level of multi-modality imaging. With the integrated MultiCellTM one-click animal bed and physiological
monitoring sytem, the studies will be seamless and referred accross all major imaging modalities: SPECT, PET, MRI and
CT from the same supplier.

nanoScan® PET/CT

MultiCellTM
anesthesia / imaging bed
3
NanoSPECT/CT ®
nanoScan® PET/MRI
 PET/CT

PET/CT Acquisition / Gantry

Touchscreen User Interface
- One interface for PET and CT
- Touch-controlled bed movements
- Online animal monitoring
- On the fly PET persistence scope function

TM
MultiCell Animal Anesthesia / Imaging Bed
- Automated positioning with µm accuracy
- Closed circuit anesthesia system integrated
into a pathogen-free imaging chamber
- One-click dockable PET / CT / SPECT / MRI
compatible imaging chamber
- Integrated heating / temperature control and
monitoring
- Respiratory and ECG gating and monitoring
®
- Compatible with NanoSPECT/CT systems

Fast and Easy Instrument Installation

- 3 x One day (Installation + Calibration + QC) for
fast routine system start up
- No need for additional lead shielding in the lab
- Compact size: 1550 x 1575 x 1510 mm
- Weight: 610 kg

4
No compromise in image quality

PET Detector Ring

- LYSO crystal full ring geometry
- 1.12 x 1.12 x 13 mm3 pixel size
- 512 ch/module flat panel sensor
- 12 cm transaxial FOV
- 0.3 mm3 spatial resolution by
Tera-TomoTM 3D PET engine

X-Ray CT System
- Wide energy range X-Ray tube
- 7 µm focal spot size
- High DQE at low dose detector
- Variable zoom (35 mm - 120 mm FOV)
- Closed cabinet X-Ray system

High Precision Gantry

- Very precise and robust rotational
bearing and drive
- Exceptionally stable gantry with
4 axis movements
- Large bore size with 16 cm opening
- Open tunnel construction: 2-way
access to the animals
- Ultra slim front cover (< 30 mm dead
space to the PET FOV) 5
 PET Subsystem

Structure
Mediso's traditions in nuclear detection technology and fine precision mechanics date back almost a century.

Leveraged by our expertise gathered across generations of patented, cutting-edge instrument innovations, the company
has designed and built the most advanced PET detector present in the market.

Mediso nanoScan® PET/CT's LYSO crystal pins are the most tightly packed (92%) and smallest in the industry,
minimizing dead detector space. Large-surface modular detector design together with the large detector ring diameter
(largest among currently available PET/CT imagers) minimizes parallax error. Mediso's patented proprietary TeraTomoTM
3D PET reconstruction algorithm offers attenuation correction, models the whole system matrix with Monte Carlo
simulations and removes parallax error. This achieves a uniform imaging resolution of ≤ 0.8 mm even at 3 cm off the
radial center. With a resolution of 0.7 mm at 1 cm off center using the very advanced TeraTomoTM 3D PET algorithm -
a value unseen in PET up to now - nanoScan® PET/CT is the first and only PET imager in the world with sub-half mm3
volumetric resolution (0.3 mm3 volumes are resolved).

The large bore size of the detector allows for a ”PET-only” or ”CT-only” mode of use in the nanoScan® PET/CT system.
High throughput imaging of larger animals is also possible. Marmoset heads or two rats can be imaged with the
standalone PET mode.

Multilayer detector logic board

RF and magnetic shielding disks

LYSO fine pixelated crystals

Interchangeable collimator
for large PET bore (16 cm)

512 ch/module flat panel sensors

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 3 TM
0.3 mm resolution by Tera-Tomo 3D PET engine

Ultra-fast PET data flow and processing

Data collected by the PET detector are sorted and processed using a proprietary, custom-designed circuit and application
specific FPGA chip. The data stream is transmitted to the image reconstruction engines, based on a cluster of GPUs.
These ultra-high performance systems enable you to simultaneously acquire and reconstruct your PET study data.

Mediso always uses state-of-the art computers and acquisition electronics to optimize data processing with the
nanoScan® PET/CT.

The combination of Mediso high-end PET detector with a very advanced 3D Teraflop Computing for Tomography:
Tera-TomoTM 3D PET reconstruction engine, also developed by Mediso leads to a PET resolution very near the physical limits.

For any tomographic detector, the acquired image is blurred and degraded due to the distortions of the imaging system.
This blurring is characterized by the Point Spread Function (PSF) or impulse response of the system.
The Tera-TomoTM 3D PET reconstruction engine incorporates both projection-space (or data-space) and image-space PSF
modeling in order to faithfully recover the original spatial resolution of the imaged objects.

Using corrections for physical factors such as detector geometry, Monte Carlo DOI estimation, object attenuation
and scatter, randoms and dead time to even positron range, a quantitative three-dimensional PET reconstruction called
Tera-TomoTM 3D PET has been developed and applied by Mediso in collaboration with prestigious Hungarian universities.

TM
Tera-Tomo 3D PET reconstruction engine principle
with on the fly system matrix generation

Monte Carlo attenuation

detector positron random
DOI and scatter
geometry range LORs and
estimation within the
dead time
object

High-speed transfer and teraflops computing speed provides you with ultra-fast reconstructions for enhanced PET study
throughput.

7
 PET Subsystem

Quantitative reconstruction with high sensitivity

This is available to every nanoScan® PET/CT user. Receptor binding potential or high precision SUV studies are robustly
performed on the nanoScan® PET/CT.

10
6
4x10
Reconstructed activity (Bq)

Absolute sensitivity (%)

6
3x10
6

6
2x10
4

1x106 2

0
0 1x106 2x106 3x106 4x106 -60 -40 -20 0 20 40 60

Measured activity (Bq) Axial distance from center (mm)

Activity concentration linearity for quantification Absolute sensitivity according to NEMA NU 4-2008: > 8.0%
Quantification error: < 3% Maximum sensitivity: > 9.0% (150-750 keV window)

Representation of quantitative accuracy of the nanoScan® PET/CT's PET component over 2 orders of magnitude. The
radioactivity measured in the syringes is well repeated by the reconstructed values.

700 µm resolution by Tera-TomoTM 3D PET engine

Below are the measured full width at half maximum resolution values of the PET subsystem in all 3 dimensions in the
FOV, (x=horizontal, y=vertical, z=axial, averaged with the RMS method) using Tera-TomoTM 3D PET. Even your routine
PET scans will bring you to the yet unseen resolution of 0.7 mm.

PET/CT fusion 1.2

1.1 0.7

1.0

0.8
RMS FWHM (mm)

0.6

0.4 Tera-TomoTM 3D PET 1.0 0.8

0.2
Mediso 0.9 nanoScan® PC
0 5 10 15 20 25 30
Radial (mm)

Point source 3D reconstructed spatial resolution

with Tera-TomoTM 3D PET reconstruction engine

CT PET
Imaging performance with Tera-TomoTM
3D PET Reconstruction Engine using 10 MBq
18
F-FDG and 30 min image acquisition
in an ultra micro-Derenzo phantom
Size of the rods: 0.7 mm – 1.2 mm
8
Exclusive PET Imaging Performance

Three plane sections of a Nude mouse bearing FaDu xenograft tumor. 34 MBq of 64Cu-labelled antibody fragment
injected i.v., imaging 24 h post injection for 20 min. Note the accumulation in kidney cortex and the tumor uptake
inhomogeneities. MIP image of the same Nude mouse.

18
F-fluoro-deoxy-glucose uptake in rat brain, PET/CT MIP image. 30 MBq of 18F-FDG injected into awake rat and imaged
50 min p.i. for 20 min.

9
 CT Subsystem

Fine structures revealed in high quality at low dose

Mediso designed a low-dose, fast but high quality zoomable cone-beam X-ray CT to complement nanoScan®'s
exceptional PET qualities. Indeed the X-ray CT alone is a whole-body imaging system on its own right. Offering a very
large detector surface and large bore, the CT of nanoScan® PET/CT can image the largest variety of animal species in
industry.

CT image quality depends on pixel number, focal point size and image zoom. To prevent trade-offs in these fields,
nanoScan® PET/CT features the industry's largest surface, largest pixel number and smallest focal point CT where the
user can choose the zoom by setting it from 1.4 to 5.0. The results are a superb soft tissue contrast, low dose to the
animal, and breath-taking details. With the highest resolution mode 9.6 micron isotropic voxels are defined whereas in
overview mode large detector surface means image stitching is avoided. Mediso InterViewTM FUSION software effectively
complements the CT by providing advanced Volume-of-Interest statistical tools of Hounsfield Units. Full radiation
shielding of the closed X-ray cabinet type approved in more than 16 countries complement the CT system. The open
back-door of the CT part ensures animal access but can also be used as a traditional closed CT.

X-ray CT of a mouse lung lobe. Three plane sections

(from left to right: transaxial, horizontal and saggital plane) of the lung lobe are
presented. Acinar walls and lung vessels are visible.
Image courtesy of CROmed Ltd. Budapest

CT images of a rat skull and a mouse whole body. Imaging time 3.4 min for the rat, 6 min for
the mouse study.
10
Image courtesy of CROmed Ltd. Budapest
 TM
MultiCell Animal Anesthesia / Imaging Bed

Continuous digital temperature control: by closed circuit airflow integrated into the wall of the chamber – avoiding the
side effect of the open airflow (dehydration of the eyes, contamination by pathogens etc.)

Embedded anesthetic gas connection: for any isoflurane system through dockable connection to the mouse /rat nose
cone via closed circuit tubes integrated into the wall of the chamber

Integrated animal head mounting: for precise and reproducible animal positioning

4D/5D imaging accessories: dockable connections for ECG and respiratory gating

Pathogen-free construction: for immuno-compromised animals

One-click connection imaging cells: for easy and fast connection of mouse /rat imaging cells to the PET/CT, PET/MRI and
SPECT/CT scanners or dual bed docking station

PrepaCell™ Preparation Station: for complete preparation of the animal before the scan (“click and scan”)

docking adapter for the scanner

one-click connection interface

transparent cover

anesthesia gas absorption by nose cone

inhalation through tooth bar

head positioning by ear bars

temperature control by integrated hot-air channels

respiratory gating by breath sensor

MultiCell™ Imaging bed

- Multimodality imaging for - Multiple mouse scanning in one scan
PET+CT+SPECT+MRI modalities (optional)

- Multipurpose applications 4D-, 5D - Multifunctioning preparation station

imaging by one-click connection for the imaging cells
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 Shared Components

Acquisition and real-time reconstruction shall be a routine – quick and comfortable

- Faster and safer acquisition and data management via state-of-the-art, high-stability and high capacity solid state disks
- The ergonomic design of the common PET/CT user interface and the touch-screen based bed movements make the
acquisition control comfortable and fast.

Control / Equipment Room

Multimodality Acquisition / Processing Workstations

Nucline Tera-Tomo - Real 3D PET

TM TM

Main Console WS Reconstruction WS

Dual monitor WS with touchscreen Supercomputer with embedded

Teraflop Computing
PET/CT acquisition and control
PET real-time 3D reconstruction
Multimodal image visualization
On the fly system matrix generation
Post processing features after acquisition
Real time image correction
DICOM 3.0 and CFR21 part 11 compliant
Post-reconstruction image manipulation
data handling
after acquisition

- Intel® Core™ i7 platform @ 3.4 GHz - Intel® Core™ i7 platform up to 4.5 GHz
- Non-stop operating WS through liquid cooling - Cutting edge computing with liquid cooling
- Safe data handling by 0,5 TB SSD - Safe raw data backup by 0.5 TB SSD
- GPU based on the fly volume rendering 1/10 Gb Ethernet - GPU cluster with 6 GB memory 10 Gb Ethernet
- Ease of use CT scout for positioning - Mainstream data transfer through dual 10 GbE
- 24” + 17” (on the gantry) LCD monitor - Realtime 64 bit OS by Linux
- Multitask 64 bit OS by MS Windows 7

Enhanced Routine and Research

Workflow
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 Fast routine / ultra precision research tool

Workflow management is designed to enhance throughput.

- High performance visualization and computational tools supported by ultra-large capacity (12 TB) on-line archiving
system
- Parallel work of two scientists is supported: while reconstruction is running on the Reconstruction WS the additional
post-processing workstation enables to analyze and quantify images from an other study.

Researcher`s Room

Multimodality Post-processing / Archiving Workstations

InterView FUSION Tera-Tomo - Post 3D PET

TM TM

Multimodality Processing WS Reconstruction WS

12 TB raw/processed data archiving Best image quality for research

Post processing and comprehensive evaluations Advanced PET post reconstruction
Quantification and kinetic modeling Detector and physical effect modeling
Advanced multimodality 3D/4D visualization On the fly image correction by GPU engine
Auto-registration of PET & CT images 3D/2D reconstructions (real-time /adaptive)
Automatic CT segmentations CT-based PET correction

- Intel® Core™ i7 platform @ 3.4 GHz

- Intel® Core™ i7 platform up to 4.5 GHz
- 12 TB fault tolerant RAID5 archiving
- Cutting edge computing with liquid cooling
- GPU engine with CUDATM based algorithms
- RAID 0.5 TB SSD for safe and fast data handling
max. 100 m - Full functionality DICOM server services 10 Gb Ethernet - GPU cluster with up to 9 GB memory
- 24 ” LCD monitor
- Mainstream data transfer through 10 GbE
- Mainstream data transfer through dual 10 GbE
- Real-time 64 bit OS by Linux
- Multitask 64 bit OS by MS Windows 7

Management
13
 Post-processing by

InterViewTM FUSION multi-modal application developed by Mediso is an essential part of nanoScan® PET/CT system. The
application provides a wide range of functionalities to evaluate preclinical PET/CT data. 2D single, orthogonal and tiled,
as well as 3D MIP and Volume Rendering viewers represent fast and flexible visualization techniques built on GPU
acceleration. Viewers provide dual, triple and quadruple fusion to accurately compare and enhance multi-modal single
and follow-up studies. Dynamic PET images together with CT can be fused, and PET images can be studied over time.
Multiple Time Activity Curves (TAC) of dynamic PET studies over time can be visualized and evaluated.

Calculations and statistical evaluations for PET are available on voxel and ROI or VOI level. A wide range of ROI and VOI
tools are available for evaluation (e.g. freehand, polygon, ellipse, rectangle, sphere, box and isocount).

CT based body-air-bone-lung segmentation methods are provided for effective PET attenuation correction.

An in-built state of the art automated rigid, affine and non-linear image registration framework provides a quick and
accurate way to superimpose different studies for comparison.

Advanced segmentation methods for different modalities, tissues and organs are available for feature extraction (e.g.
lung, vessel, bone, CT body-air-bone-lung, PET lesion detection)

Arithmetic operations help differentiating follow-up studies on voxel level by several methods (e.g. sum, difference,
absolute difference, average, minimum, maximum, multiply).

Visualization of 18F-fluoro-deoxy-glucose uptake in rat brain. After the intravenous injection of 30 MBq of 18F-FDG rats
were kept awake for 50 min. The static PET image was collected during 20 min in isoflurane anesthesia. Cortical gyri,
thalamus, cerebellum and brain stem uptake is visualized. Note the FDG uptake in brown fat tissue over the scapular
region. Image courtesy of Karolinska Institute.

To enable researchers with all necessary image visualization, analysis and quantification tools, Mediso offers a uniquely
complete and flexible software package for the nanoScan® PET/CT system. Beside Mediso's InterViewTM FUSION both
inviCRO's VivoQuant providing advanced 3D segmentation, data sharing and atlas tools and PMOD's industry
standard pharmacokinetic analysis and post-processing modules are supported.
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Applications

Dr. Ralf Bergmann

Institut für Radiopharmazie
Radiopharmazeutische Biologie
Helmholtz-Zentrum Dresden-Rossendorf

„I am very satisfied with the results obtained on our

Mediso nanoScan® PET/CT system. A very good
sensitivity and stunning PET/CT resolution are combined
with easy animal access. Our high throughput
radiopharmaceutical development tasks and tumour
biology work are well supported by the nanoScan®.
It is a flexible and user-friendly PET/CT system with no
compromise on image quality and functionality.“

input, response and fit response contributions cg ~ fdgmodel(tt, ca, metfrac, k1, k2, k3, k4, fbv, delay)

Fit: k1 = 0.4423, k2 = 0.06304, k3 = 0.02874, fbv = 0.03741 Fix: k4 = 0, delay = 0, ca = 8.384e+04, metfrac = 0
5e+05

5e+05

5e+05

arterial input l free l l

data
tissue response bound fit l

95% conf. lim.

fbv
total
l l
l
4e+05

4e+05

4e+05

l l
l

l l
l
3e+05

3e+05

l l
input + response (Bq/ml)

3e+05

l
response (Bq/ml)

response (Bq/ml)

l l
l

l l
l

l l
2e+05

2e+05

l
2e+05

l
ll ll l l l l
l l l l l
l l l
ll l
ll ll
l l l l l l l
l l l
l residuals
ll lll 0 10 20 30 40 50
ll
ll lll l
l ll
l
l l l
llll ll
1e+05

1e+05

ll
1e+05

l l
ll ll ll
l
20000

l l l
l l l
l l
l l l

l l
0

l l l l
l l
l
l
-20000

l l
0e+00

0e+00

ll ll
0e+00

l ll
l l
ll ll
ll
ll
l
l
ll l
l
ll
l
ll
l
ll
ll
l
l llllllll l l l l l l l l
l
llll

0 10 20 30 40 50
0 10 20 30 40 50 0 10 20 30 40 50
blood, myocard time (min) time (min) blood, myocard time (min)

Time-activity curves of heart myocardial [18F]FDG uptake.

Data and diagrams courtesy of Helmholtz-Zentrum Dresden Rossendorf, Germany

[64Cu]Cu-NOTA-AntiEGFR-Fab whole-body imaging of a [68Ga]Ga-NOTA-microspheres PET/CT study on the lungs

NMRI Nu/Nu mouse with FaDu tumor xenograft 48 of a Wistar rat. 40 MBq of i.v. injected activity imaged
hours post i.v. injection of 34 MBq labeled Fab. Imaging for 20 min.
duration 30 min, imaged actual activity cca. 3 MBq. Image courtesy of Helmholtz-Zentrum Dresden
Three plane sections. Besides heterogeneous uptake in Rossendorf, Germany
the tumor, kidney cortex and liver is visible, too.
Image courtesy of Helmholtz-Zentrum Dresden
Rossendorf, Germany 15
Conformance Statement

Product design, development, production and services comply with ISO

9001:2001 and with ISO 13485:2004.

The nanoScan® multimodality molecular imaging system conforms to EC

Directive 93/42/EEC; Annex II, Article 3 Full Quality Assurance System
Medical Devices Design and safety testing has been performed in
accordance with IEC 60601-1 and IEC 60601-1-2 EMC standards.

Safety labels are attached to appropriate places on equipment and

appear in all operation manuals.

The supplied software conforms to DICOM and CFR 21 part 11 standard.

The technical information provided here is not a detailed specification.

For exact details and up to date information please contact your local
distributor or Mediso Medical Imaging Systems.

nanoScan is registered trademark of MEDISO Medical Imaging Systems.

®

NuclineTM, InterViewTMFUSION, Tera-TomoTM 3D PET, MultiCellTM,

PrepaCellTM are trademarks of MEDISO Medical Imaging Systems.

coreTM i7 is trademark of Intel.

®
Windows is registered trademark of Microsoft.
®
NanoSPECT/CT is registered trademark of BIOSCAN.

CUDATM is trademark of NVIDIA.

This product was partially established by the support of the National

Development Agency of Hungary using funds of the Research and
Technology Fund (code: TeraTomo).

MEDISO Medical Imaging Systems

1022 Budapest, Alsótörökvész 14. Hungary
Phone.: +36-1-399-3030
Fax.: +36-1-399-3040
E-mail: [email protected]
Web: www.mediso.com
1008

MEDISO reserves the right to change data without notice © MEDISO 2012. Printed in Hungary NPCB 02/12