TY  - THES
A1  - Triphan, Simon
T1  - T1 und T2*-Quantifizierung in der menschlichen Lunge
T1  - T1 and T2* quantification in the human lung
N2  - In dieser Arbeit werden für die Anwendung in der menschlichen Lunge
optimierte Methoden zur Bestimmung von T1- und T2*-Karten diskutiert:
Dc-Gating ermöglicht die Quantifizierung in freier Atmung, wobei für die
T1-Quantifizierung mittels Inversion Recovery eine Korrektur des dc-Signals
entwickelt wurde. Dies hat den Vorteil, dass Parameterkarten aus mehreren
Messungen anhand ihrer dc-Signale passend überlagert werden können.  Da T1
und T2* auf unterschiedliche Art und Weise von der Sauerstoffkonzentration
abhängen, verbessert dies die Möglichkeit, ΔT1- und ΔT2*- Differenzkarten aus
Messungen mit unterschiedlichen O2-Konzentrationen im Atemgas zu erstellen.

Die Parameterquantifizierung ist in erster Linie für die Beobachtung von
Krankheitsverläufen interessant, da T1 und T2* absolute, vergleichbare Zahlen
sind. Da T2* deutlich vom Atemzustand abhängt, ist es auch hierfür sinnvoll,
durch Gating identische Atemzustände abzubilden. Um die unterschiedlichen
Einflüsse des Sauerstoffs auf T1 und T2* besser vergleichbar zu machen, wurde
in dieser Arbeit weiterhin eine kombinierte Messung für beide Parameter
implementiert: Da auch diese in freier Atmung stattfindet, profitieren nicht
nur die Differenzkarten von der Überlagerung der Bilder, sondern auch der
Vergleich der ΔT1- und ΔT2*-Karten untereinander.

Messungen mit einer konventionellen kartesischen Methode an COPD-Patienten
unter Raumluft- und 100% Sauerstoffatmung ergaben bei Verwendung identischer
Atemmasken ein deutlich geringeres ΔT1 als in gesunden Probanden.  Dass T1 in
der Lunge nicht nur von der Sauerstoffkonzentration sondern auch von der
Gewebezusammensetzung und insbesondere auch dem Blutvolumenanteil abhängt,
zeigte sich hierbei aber auch an den bei COPD im Mittel sehr viel kürzeren
T1-Zeiten bei Raumluft. Die aufgrund emphysematischer Veränderung noch
zusätzlich reduzierte Protonendichte im Parenchym kranker Lungen macht diese
Messungen allerdings besonders schwierig.  

Die oben erwähnten Optimierungen der T1-Quantifizierung zielen daher auch
darauf ab, das Signal aus der Lunge zu maximieren, um Patientenmessungen
einfacher zu machen: Messungen in freier Atmung sind für Patienten nicht nur
einfacher, sondern erlauben effektiv auch längere Messzeiten. Insbesondere
wurde aber durch die Entwicklung einer radialen Methode die Echozeit zur
Messung reduziert, um die kurze T2*-Zeit in der Lunge auszugleichen.
Schließlich wurde durch Implementation einer 2D UTE Sequenz die Messung bei
der kürzesten vom Scanner erlaubten Echozeit ermöglicht.

Die Messungen bei ultrakurzen Echozeiten in Probanden zeigten allerdings
deutlich kürzere T1-Zeiten als die zuvor gefundenen oder in der Literatur
dokumentierten. In weiteren Experimenten wurde das sichtbare T1 zu mehreren
Echozeiten mit Hilfe der zur kombinierten Quantifizierung entwickelten
Methode bestimmt. Dabei ergab sich eine Zunahme des gemessenen T1 mit der
Echozeit. Aus diesem Verhalten sowie den gefundenen kürzesten und längsten T1
lässt sich schließen, dass das intra- und extravaskuläre Lungenwasser, also
Blut bzw. das umgebende Gewebe, mit unterschiedlichen T1- und T2*-Zeiten zum
Signal und damit auch dem effektiven T1 beitragen.

Dass das TE der Messung die Gewichtung dieser Kompartimente bestimmt, hat
dabei mehrere Auswirkungen: Einerseits bedeutet dies, dass beim Vergleich von
T1-Messungen in der Lunge stets auch das TE mitbetrachtet werden muss, bei
dem diese durchgeführt wurden. Andererseits lässt sich die Möglichkeit, die
Messung auf die unterschiedlichen Kompartimente abzustimmen, potentiell
ausnutzen, um zusätzliche diagnostische Informationen zu gewinnen: Da T1 vom
Blutvolumenanteil und der Gewebezusammensetzung abhängt, könnte dieser Effekt
helfen, diese beiden Einflüsse zu differenzieren.

Während die in dieser Arbeit beschriebenen Experimente die TE-Abhängigkeit
des sichtbaren T1 in Probanden aufzeigen, liefern sie allerdings noch keine
genaue Erklärung für die möglichen Ursprünge dieses Effekts. Um diese weiter
zu untersuchen, könnten allerdings gezielte Phantom- und in vivo-Experimente
Aufschluss geben: Ein Aufbau, der die Feldverzerrung durch luftgefüllte
Alveolen in Lösungen mit entsprechenden verschiedenen Suszeptibilitäten
nachbildet, reduziert den Unterschied zwischen den Kompartimenten auf T1 und
χ. Eine in vivo-Messung mit möglichst großer Differenz zwischen Ex- und
Inspiration hingegen könnte den Einfluss der Abstände der Kompartimente vom
Gasraum aufzeigen, da die Alveolarwände in tiefer Inspiration am weitesten
gedehnt und daher am dünnsten sind.
N2  - In this work, methods for the local measurement of T1 and T2* maps optimized
for the application in the human lungs are discussed: Quantification during
free breathing was enabled by applying dc-gating, where a correction for the
dc-signal acquired during T1-quantification using a inversion recovery was
introduced. This is especially useful to achieve parameter maps in identical
breathing states from multiple measurements using their dc-signals. Since T1
and T2* depend on the oxygen concentration through different mechanisms, this
is especially interesting to produce ΔT1- and ΔT2*-difference maps at varying
O2-concentrations in the breathing gas.

Parameter quantification is primarily interesting for the monitoring of the
courses of disease or therapy since T1 and T2* are absolute, comparable
numbers. As T2* depends significantly on the respiratory state, ensuring
identical states via gating is relevant there as well. To further improve the
comparison of oxygen influence on T1 and T2* a method for the combined
measurement of both parameters was implemented: Since this is also employs
gating, not only the difference maps benefit from image coregistration, but
the comparison of the ΔT1 and ΔT2* maps to each other as well.

Measurements using the conventional cartesian method on COPD patients under
room air and pure oxygen conditions resulted in much lower ΔT1 than in
healthy volunteers when using identical oxygen masks. The much lower average
T1 times at room air found there demonstrate that T1 in the lungs not only
depends on the oxygen concentration but also on tissue composition and
especially the blood volume fraction. Proton densities that were reduced even
further due to emphysematous destruction made these measurements additionally
difficult.

Accordingly, the optimizations for T1 quantification mentioned above are
intended to maximize signal from the lung parenchyma to improve patient
measurements: Measurements during free breathing are not only easier for
patients but effectively also allow for longer acquisition times. In
particular the developement of a radial method provides a shorter echo time
to help compensate for the short T2* in the lungs. Finally, the
implementation of a 2D UTE sequence enables the measurement at the shortest
echo time available on the scanner hardware.

However, the measurements at ultra short echo times in volunteers showed
significantly shorter T1 times than those found previously and those reported
in the literature. In further experiments, the observable T1 was determined
at multiple echo times using the method developed for simultaneous
quantification. This revealed a gradual increase of the measured T1 with the
echo time. From this behaviour as well as the shortest and longest times
found, it can be concluded that the intra- and extravascular compartments of
lung water, essentially blood and the surrounding tissue, contribute with
different T1 and T2* times to the MR signal and thus also the effective T1.

That the echo time of the measurement determines the weighting of these
compartments has multiple consequences: Firstly, this means that when
comparing T1 measurements in the lungs, the echo time that was used to
acquire them also has to be considered. Secondly, the possiblity to focus the
measurement on these different compartments might be used to gain additional
diagnostic information: Since T1 depends on blood volume content and tissue
composition, this effect might help to differentiate these two influences.

While the experiments described in this work demonstrate the echo time
dependence of the observed T1 in volunteers, they do not yet provide an
explanation for the exact origins of this effect. To examine these further,
appropriate phantom and in vivo experiments could be insightful: A phantom
design that simulates the field distortion caused by air-filled alveoli in
solutions with suitable susceptibilites would reduce the difference between
the compartments to T1 and χ. A in vivo measurement with an especially large
difference between ex- and inspiration could help to show the influence of
the distance of the compartments from the gas space, since the alveolar walls
are most dilated and thus thinnest during deep inspiration.
KW  - Kernspintomografie
KW  - Lunge
KW  - T2*-Relaxation
KW  - T1-Relaxtion
KW  - funktionelle Lungenbildgebung
KW  - MRT der Lunge
KW  - Spin-Gitter-Relaxation
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-139621
ER  - 
TY  - JOUR
A1  - Triphan, Simon M. F.
A1  - Jobst, Bertram J.
A1  - Anjorin, Angela
A1  - Sedlaczek, Oliver
A1  - Wolf, Ursula
A1  - Terekhov, Maxim
A1  - Hoffmann, Christian
A1  - Ley, Sebastian
A1  - Düber, Christoph
A1  - Biederer, Jürgen
A1  - Kauczor, Hans-Ulrich
A1  - Jakob, Peter M.
A1  - Wielpütz, Mark O.
T1  - Reproducibility and comparison of oxygen-enhanced T\(_1\) quantification in COPD and asthma patients
JF  - PLoS ONE
N2  - T\(_1\) maps have been shown to yield useful diagnostic information on lung function in patients with chronic obstructive pulmonary disease (COPD) and asthma, both for native T\(_1\) and ΔT\(_1\), the relative reduction while breathing pure oxygen. As parameter quantification is particularly interesting for longitudinal studies, the purpose of this work was both to examine the reproducibility of lung T\(_1\) mapping and to compare T\(_1\) found in COPD and asthma patients using IRSnapShotFLASH embedded in a full MRI protocol. 12 asthma and 12 COPD patients (site 1) and further 15 COPD patients (site 2) were examined on two consecutive days. In each patient, T\(_1\) maps were acquired in 8 single breath-hold slices, breathing first room air, then pure oxygen. Maps were partitioned into 12 regions each to calculate average values. In asthma patients, the average T\(_{1,RA}\) = 1206ms (room air) was reduced to T\(_{1,O2}\) = 1141ms under oxygen conditions (ΔT\(_1\) = 5.3%, p < 5⋅10\(^{−4})\), while in COPD patients both native T\(_{1,RA}\) = 1125ms was significantly shorter (p < 10\(^{−3})\) and the relative reduction to T\(_{1,O2}\) = 1081ms on average ΔT\(_1\) = 4.2%(p < 10\(^{−5}\)). On the second day, with T\(_{1,RA}\) = 1186ms in asthma and T\(_{1,RA}\) = 1097ms in COPD, observed values were slightly shorter on average in all patient groups. ΔT\(_1\) reduction was the least repeatable parameter and varied from day to day by up to 23% in individual asthma and 30% in COPD patients. While for both patient groups T\(_1\) was below the values reported for healthy subjects, the T\(_1\) and ΔT\(_1\) found in asthmatics lies between that of the COPD group and reported values for healthy subjects, suggesting a higher blood volume fraction and better ventilation. However, it could be demonstrated that lung T\(_1\) quantification is subject to notable inter-examination variability, which here can be attributed both to remaining contrast agent from the previous day and the increased dependency of lung T\(_1\) on perfusion and thus current lung state.
KW  - Medicine
KW  - Chronic obstrusive pulmonary disease
KW  - Asthma
KW  - Oxygen
KW  - Magnetic resonance imaging
KW  - Breathing
KW  - Pulmonary imaging
KW  - Protons
KW  - Diagnostic medicine
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171833
VL  - 12
IS  - 2
ER  - 
TY  - JOUR
A1  - Jobst, Bertram J.
A1  - Wielpütz, Mark O.
A1  - Triphan, Simon M.F.
A1  - Anjorin, Angela
A1  - Ley-Zaporozhan, Julia
A1  - Kauczor, Hans-Ulrich
A1  - Biederer, Jürgen
A1  - Ley, Sebastian
A1  - Sedlaczek, Oliver
T1  - Morpho-Functional 1H-MRI of the Lung in COPD: Short-Term Test-Retest Reliability
JF  - PLOS ONE
N2  - Purpose 
Non-invasive end-points for interventional trials and tailored treatment regimes in chronic obstructive pulmonary disease (COPD) for monitoring regionally different manifestations of lung disease instead of global assessment of lung function with spirometry would be valuable. Proton nuclear magnetic resonance imaging (1H-MRI) allows for a radiation-free assessment of regional structure and function. The aim of this study was to evaluate the short-term reproducibility of a comprehensive morpho-functional lungMRI protocol in COPD.

Materials and Methods 
20 prospectively enrolled COPD patients (GOLD I-IV) underwent 1H-MRI of the lung at 1.5T on two consecutive days, including sequences for morphology, 4D contrast-enhanced perfusion, and respiratory mechanics. Image quality and COPD-related morphological and functional changes were evaluated in consensus by three chest radiologists using a dedicated MRI-based visual scoring system. Test-retest reliability was calculated per each individual lung lobe for the extent of large airway (bronchiectasis, wall thickening, mucus plugging) and small airway abnormalities (tree in bud, peripheral bronchiectasis, mucus plugging), consolidations, nodules, parenchymal defects and perfusion defects. The presence of tracheal narrowing, dystelectasis, pleural effusion, pulmonary trunk ectasia, right ventricular enlargement and, finally, motion patterns of diaphragma and chest wall were addressed. 

Results 
Median global scores [10(Q1:8.00; Q3:16.00) vs. 11(Q1:6.00; Q3:15.00)] as well as category subscores were similar between both timepoints, and kappa statistics indicated "almost perfect" global agreement (\(\kappa\)= 0.86, 95%CI = 0.81-0.91). Most subscores showed at least "substantial" agreement of MRI1 and MRI2 (\(\kappa\)= 0.64-1.00), whereas the agreement for the diagnosis of dystelectasis/effusion (\(\kappa\)= 0.42, 95%CI = 0.00-0.93) was "moderate" and of tracheal abnormalities (\(\kappa\)= 0.21, 95%CI = 0.00-0.75) "fair". Most MRI acquisitions showed at least diagnostic quality at MRI1 (276 of 278) and MRI2 (259 of 264).
 
Conclusion 
Morpho-functional 1H-MRI can be obtained with reproducible image quality and high short-term test-retest reliability for COPD-related morphological and functional changes of the lung. This underlines its potential value for the monitoring of regional lung characteristics in COPD trials.
KW  - capability
KW  - obstructive pulmonary disease
KW  - quantitative computed tomography
KW  - cystic fibrosis
KW  - proton MRI
KW  - perfusion
KW  - emphysema
KW  - CT
KW  - agreement
KW  - dysfunction
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151365
VL  - 10
IS  - 9
ER  -