Добавил:

Sekretar kiopkiopkiop18@yandex.ru t.me/Prokururor I Вовсе не секретарь, но почту проверяю Опубликованный материал нарушает ваши авторские права? Сообщите нам.

Вуз:

Ростовский Государственный Медицинский Университет

Предмет:

Медицина общая

Файл:

Книга_5776_Библиотеки_им_академика_М_И_Перельмана

.pdf

Скачиваний:

Добавлен:

30.08.2026

Размер:

53 Мб

Скачать

☆

<<< < Предыдущая 7 8 9 10 11 12 13 14 15 16 17 1819 / 5019 20 21 22 23 24 25 26 27 28 29 30 31 > Следующая >>>

159Arterial Pathology

Valdueza et al., Neurosonology and Neuroimaging of Stroke: A Comprehensive Reference, Second Edition (ISBN 978-3-13-141872-2), copyright © 2017 Thieme Medical Publishers All rights reserved. Usage subject to terms and conditions of license.

BAV2-VA-LV2-VA-R

Fig. A5.140 Synopsis of VA and BA ﬂ ow patterns in intracranial posterior circulation occlusion depending on the location of the occlusion. Both VAs are well developed. (A) P1-PCA occlusion—no ﬂ ow alteration. (B) Top of the basilar artery occlusion—no signiﬁ cant VA ﬂ ow alterations. No or only mild BA ﬂ ow reduction. (C) Midbasilar occlusion—distinct prestenotic ﬂ ow alteration in both VAs and even more in the BA, if detectable. (D) Unilateral V4-VA occlusion distal of the PICA origin—only moderate ipsilateral prestenotic VA ﬂ ow alteration as the blood ﬂ ow into the PICA is preserved. Note that a normal ﬂ ow signal may also be present. Normal BA ﬂ ow. (E) Unilat- eral V4-VA occlusion proximal to the PICA origin—severe prestenotic VA proﬁ le alteration without diastolic ﬂ ow. Slightly increased contralateral VA ﬂ ow velocities may also be observed in D.

is used with only the transforaminal insonation approach the diagnostic speciﬁ city of 96% is high but the sensitiv- ity of 60% is low (Demchuk et al 2000a). Echo contrast agents, the transtemporal insonation at least of the PCA, and the extracranial VA examination are, however, of great importance (Kermer et al 2006). An acute proximal BA occlusion will always result in prestenotic ﬂ ow alter- ations with increased pulsatility in both extracranial VAs (Fig. A5.137). Transtemporal insonation in the axial plane then shows a ﬂ ow into the PCA via a PCoA or a fetal-type PCA if present (Fig. A5.138). The distal BA segment may then, transtemporally or transforaminally, reveal a retrograde ﬂ ow derived from one or both P1-PCA and PCoA segments (Fig. A5.139). A distal occlusion at the top of the BA, however, may leave both VA proﬁ les and even the proximal BA signal almost unchanged (Fig. A5.140). This is explained by the numerous arteries that originate from the proximal segments (AICA and perforator arteries) and which may result in a nearly unchanged peripheral ﬂ ow resistance, especially if the SCAs remain open and antegradely perfused. Therefore, apparently normal VAs

CBA

Fig. A5.141 (A) DSA, selective right VA injection, p.a. view revealing a distal VA occlusion at the V3–V4 junction (arrow). Note small collaterals (arrowheads). (B) DSA, selective left VA injection, lateral view revealing a proximal BA occlusion (arrowhead). Note the marked signal of the PICA (large arrow) ﬁ lling the SCA via leptomeningeal anastomoses (curved arrow). The distal and mid BA is assumed to be retrograde perfused (short arrow). (C) DSA, selective left VA in- jection, p.a. view revealing that the left PICA (arrow) provides the blood supply for both cerebellar hemispheres via cortical anastomoses. Note that the signals are partly superimposed, impeding a clear view of vessel anatomy. In this case, the right PCA territory was perfused by a fetal-type PCA and the left PCA territory by leptomeningeal anastomoses of the ipsilateral MCA and ACA (both not shown). (D,E) Extracranial duplex, V2-VA insonation of the right (D) and left (E) V2-VA in the longitudinal insonation plane, color-mode imaging and corresponding Doppler spectra. Both V2-VA had normal diameter (right 3.4 mm, left 3.8 mm). The right V2-VA had a high pulsatile ﬂ ow signals (23/3 cm/s) indicative of a severe distal obstruction. The left V2-VA appeared normal despite the proximal BA occlusion b e c a u s e o f t h e c o l l a t e r a l p a t h w a y s ( 4 3 / 1 4 c m / s ) .

and a normal proximal BA ﬂ ow signal are not suﬃ cient to exclude occlusion at the top of the BA. Additional axial and coronal transtemporal insonation may help to overcome this problem if the distal BA can be visualized. Tra nsc rania lly, u ndi stu rbe d ﬂ ow signals in one or both PCAs without the presence of a fetal-type PCA variation strongly argues against a distal BA or a more proximal BA occlusion. However, in the rare cases of a chronic proximal or midpart BA occlusion a leptomeningeal collateral ﬂ ow from the PICA to the SCA territory may backﬁ ll the distal BA. In this occasion ﬂ ow patterns of the extra- and intra cranial segments of one or both VAs may appear almost normal. Depending on the presence of a fetal-type PCA or a marked PCoA, the ﬂ ow signals of the PCA may be variable with a retrograde P1-PCA or antegrade normal or poststenotic P2-PCA (Fig. A5.141). In limited insonation conditions, digital tapping of VAs and ICAs under simultaneous PCA ﬂ ow analysis might additionally help to identify the intracranial ﬂ ow pattern. Complete BA occlusion can in most cases be excluded if VA tapping at the atlas loop leads to a visible oscillation eﬀ ect within the PCA. Only in chronic midbasilar occlusion may the obstruction be surpassed by anastomoses between the PICA and SCA as mentioned above. It is important to note that TCCS cann ot exclude the presence of a thrombus that is fragmented or adherent to the vessel wall. Sonography

160 5 Vascular Pathology

Fig. A5.142 (A) TCCS, transforaminal approach, B-mode image. Note the foramen magnum (white circle) and the clivus (arrowhead). Note also the marked hyperechoic structure surrounding the posterior arch of the atlas which represents VA calciﬁ cation (arrows). (B) CCT bone window showing severe calciﬁ ed V4-VAs during their passage in the foramen magnum (arrows). (C,D) TCCS, transforaminal approach, color-mode and corresponding Doppler spectra conﬁ rming a proximal V4-VA stenosis at a depth of 54 mm and a n g l e - c o r r e c t e d h i g h ﬂ ow velocities of 245/81 cm/s.

should therefore only be performed if it causes no delay for the routine CTA, MRA, or DSA diagnostics, or if there is a need for follow-up investigations. For further details, see Case 21.

CBA

Fig. A5.143 (A) 3D TOF-MRA, coronal MIP revealing a signal de- crease and lumen irregularities in the V4-VA distal of the PICA (arrowhead). (B) Contrast-enhanced MRA, coronal MIP shows less vessel irregularities and was thought to exclude V4-VA stenosis. Note again the PICA (arrowhead) (C,D) TCCS, transforaminal approach, color-mode and corresponding Doppler spectra revealing a disturbed ﬂ ow with increased ﬂ ow velocities (199/56 cm/s) indi- cating a >50% distal V4-VA stenosis. No poststenotic ﬂ ow pattern was seen in the downstream vessels (not shown).

VA Stenosis

The V4-VA, together with the carotid siphon, is the preferential site for atherosclerotic intracranial lesions and stenoses are therefore common. In a multicenter intracranial stent registry of 388 symptomatic patients, 18% had stenoses at this location (Kurre et al 2010). The intracranial V4-VA segments are generally easily accessible via the transforaminal approach. Stenoses can be assessed by analyzing ﬂ ow velocity, proﬁ le disturbanc- es, and pre- and poststenotic ﬂ ow patterns. Velocity cut- oﬀ values for ≥50% and <50% stenosis are given in Fig. A5.92. If possible, a pre- and post-PICA located stenosis should be distinguished (Fig. A5.142, Fig. A5.143, Fig. A5.144). A hemodynamically relevant stenosis leads to secondary signs mainly with a poststenotic ﬂ ow pattern in the downstream vessels (Tian et al 2006). It is important to note that a stenosis in a hypoplastic post-PICA V4-VA segment might not lead to a detectable increase of ﬂ ow velocity. For further details about VA stenosis, see Case 8 and Case 16.

VA Occlusion

Flow signals in V4-VA occlusion strongly depend on the site of the occlusion, mainly in their relation to the origin of the PICA (proximal or distal). Similar to the distal extracranial VA occlusion, a proximal intracranial occlusion below the origin of the PICA results in a prestenotic extracranial VA ﬂ ow pattern without diastolic ﬂ ow (Fig. A5.145). In this case a retrograde intracranial VA ﬂ ow may be found indicating a retrograde ﬁ lling of the ipsilateral PICA

Fig. A5.144 (A) 3D TOF-MRA, coronal MIP, 180° rotated to correspond with the ultrasound image revealing a distal V4-VA lumen reduction (arrow). The PICA is indicated with an arrowhead. (B,C) TCCS , tr ansfora mina l ap proa ch, col or-m ode an d corre sponding Doppler spectra, revealing an aliasing and a disturbed ﬂ ow with increased ﬂ ow velocities (173/70 cm/s) at a depth of 53 mm indi- cating a >50% distal V4-VA stenosis. Note that in this patient with a slender neck circumference the distal V4-VA was located at a depth of 53 mm. The BA origin in this case was located at a depth of 60 mm.

(Fig. A5.146). An important diﬀ erential diagnosis of this extracranial ﬁ nding is a hypoplastic VA which can usually be ruled out by measuring the vessel diameter within the V2-VA segment. Furthermore, even in a hypoplastic VA a residual diastolic ﬂ ow component should be present.

Occlusions distal to the PICA origin are diﬃ cult to de-

tect as they may have similar ﬂ ow signals to the physio- logic anatomic variant of a PICA-ending VA. In that case, however, a small-diameter V2-VA is usually present as

161Arterial Pathology

V2-VA R V2-VA L

Fig. A5.145 Pre-PICA V4-VA occlusion. Middle: 3D TOF-MRA, coronal view, showing a left-sided V4-VA occlusion. The residual distal VA vessel stump (arrow) conﬁ rms that no hypoplastic variant is present. Note also a marked ipsilateral AICA (arrowhead). Left and right: Extr acran ial duplex, V2-VA insonation in the longitudinal insonation plane, colormode imaging and corresponding Doppler spectra. Diameter of V2-VA is 4.2 mm on the right and 2.5 mm on the left. Note the normal ﬂ ow signal on the right V2-VA (45/18 cm/s) but a prestenotic left V2-VA with low (23 cm/s) systolic ﬂ ow component and missing diastolic com- ponent, compatible with a pre-PICA V4-VA occlusion.

ABC

FED

Fig. A5.146 Retrograde V4-VA in left pre-PICA dissecting occlusion of V3-VA. (A) 3D TOF-MRA, coronal view, revealing a short segment of the left V4-VA (arrow) which was initially misinterpreted as a distal V4-VA occlusion. (D) Ce-MRA, coronal view. Ce images revealed an almost normal intracranial left-sided VA (arrowheads). Note the distal ending of the dissecting V3-VA occlusion (large arrowhead). (B,C) TCCS, transforaminal approach, color-mode and corresponding Doppler spectra revealing a normal right V4-VA color and Doppler signal (ﬂ ow velocity 89/31 cm/s). (E,F) TCCS, transforaminal approach, color-mode and corresponding Doppler spectra revealing a retrograde left V4-VA ﬂ ow (ﬂ ow velocity 45/22 cm/s).

the V2-VA does not contribute to the perfusion of the PCA territory. An occlusion distal to the PICA origin can otherwise be assumed if a low velocity signal with high PI is seen in a normal-diameter vessel (Fig. A5.147). In case of a brainstem ischemia a distal VA occlusion seems even more likely (for further reading, see Case 41). It is important to note that the presence of an end-diastolic ﬂ ow is always indicative of brain-supplying chara cter of this ﬂ ow signal. A lumen diameter >2.8 mm and a diameter-ratio (diameter of contralateral VA divided by diameter of target VA) <1.4 argue strongly in favor of VA occlusion distal of the PICA and against a VA ending as the PICA, which are otherwise both characterized by a low mean velocity <18 ms (Saito et al 2004) (for further reading see also Case 19 and Case 35).

Collateral Pathways

Activation of collateral pathways has, along with recanalization, the greatest prognostic importance in acute ischemic stroke (D. Liu et al 2014, Miteﬀ et al 2009). The main underlying mechanism for the development of collateral function is the change in perfusion pressure caused by blood vessel obstruction. As the arterial vascular system is free of valves, the bloodstream may follow the direction of need, only limited by the individual anatomic situation. The more proximal an occlusion occurs, the easier it is for collaterals to compensate for it. Therefore, a major intracranial occlusion will only rarely occur without clinical manifestation of stroke. Extracranial occlusions are less likely to endanger the patient, at least from a hemo dynamic point of view. In the following

V2-VA R V2-VA L

Fig. A5.147 Post-PICA V4-VA occlusion. Middle: 3D TOF-MRA, coronal view, showing a left-sided distal V4-VA occlusion (arrow). The PICA is clearly visible (arrowhead). Left and right: Extracranial duplex, V2-VA insonation in the longitudinal insonation plane, color-mode imaging and corresponding Doppler spectra. Normal diameter of V2-VA on both sides (right 4.0 mm, left 3.6 mm). Note the normal ﬂ ow signal on the right V2-VA (50/21 cm/s) and the slightly higher pulsatility on the left V2-VA (43/9 cm/s) compatible with a distal post-PICA V4-VA occlusion.

sections we explain potential intracranial collateral pathways and the pattern of collateral ﬂ ow in extra- and in- tracranial occlusive processes assessed by ultrasound and by the other available neuroimaging modalities. Finally, we discuss the clinical relevance of collateral circulations.

162 5 Vascular Pathology

300

Fig. A5.148 (A) Schematic showing the normal anatomy of the brain-supplying arteries with a normal blood volume ﬂ ow (BVF) in both ICAs and VAs assuming a global blood volume ﬂ ow of 750 mL/min (in the example, 300 mL/min for each ICA and 75 mL/min for each VA). (B) In unilateral CCA and bilateral VA occlusion the total BVF of 750 mL/min or slightly less will run through the remaining ICA. The ECA may contribute to brain perfusion via the OA. (C) In unilateral VA a nd bil ate ral CCA occ lus ion th e to tal BV F ha s to be com pen sat ed b y the remaining VA. More complex collateral pathways may be present.

~750

Intracranial Collateral Pathways

Primary Collaterals (ACoA and PCoA)

The cerebral arterial circle (circle of Willis) is the main intracranial distributor of blood. Until the introduction of dynamic diagnostic tests in vivo, the analysis of its importance and regulatory function was rather limited and restricted to postmortem analysis of anatomy and vessel diameter.

The unpaired ACoA and both PCoAs are the most important control variables of the circle of Willis, also called ﬁ rst-order collaterals in the case of hemodynamically relevant steno-occlusive disorders proximal to the communicating arteries. If normally developed, these arteries together form a closed and therefore functional circle. Ideally their diameter approximates the diameters of the other basal cerebral arteries (see Fig. A2.17). Only then can a proximal arterial occlusion result in collateral ﬂ ow without impairment of blood ﬂ ow. Even in a constellation of a three-vessel occlusion—for example, involvement of one VA and both ICAs (Wróblewski et al 1997) and even of one VA and both CCAs (Karaköse et al 2002)—the remaining VA may be able to provide the blood supply for the whole brain via the circle of Willis, provided that a normal heart function is present (Fig. A5.148). The above cases are exceptionally rare; however, more frequently bilateral ICA occlusions can be found which are also often well compensated (for further details, see Case 12). In the latter constellation, one or both PCoAs are activated to maintain a suﬃ cient cerebral perfusion. A collateral ﬂ ow via the ACoA will then only occur if only one PCoA provides the blood supply for both sides of the anterior circulation. A predominantly PCoA-derived blood ﬂ ow into the MCA and ACA may also occur in unilateral ICA occlusion. The main collateral ﬂ ow pattern is, however, via the so-called “cross-ﬂ ow” from the contralateral ICA, in which the blood ﬂ ows from the contralateral A1-ACA

Fig. A5.149 Right extracranial ICA occlusion. (A) DSA, selective left ICA ﬁ lling, posteroanterior view. A cross-ﬂ ow from the left ICA via A1-ACA, ACoA (arrow) and retrograde right A1-ACA into the right MCA is seen. (B) DSA, selective left VA ﬁ lling, posteroanterior view. Note the collateral ﬂ ow via the right PCoA (arrow) into the right MCA territory. Note the retrograde ﬁ lling of the right VA (arrows), merely induced by the pressure injection of the contrast agent during DSA and not to be interpreted as a steal phenomenon.

via the ACoA and the retrograde ipsilateral A1-ACA toward the MCA (Henderson et al 2000). A combination of both primary collateral ﬂ ow patterns is also often ob- served. DSA mostly overlooks this phenomenon because of the selective injection of the contrast agent into the ICA and VA, while TCCS reveals ﬂ ow separation from the PCoA into the MCA and from the ACoA into the ACA. This observation has been impressively conﬁ rmed by spin-la- beling MRA in patients with symptomatic ICA occlusion, in whom the MCA territories were mainly supplied via the vertebrobasilar arteries and the ACA territories by the contralateral ICA (van Laar et al 2007). A precondition for these two mechanisms is not only the existence of functioning communicating arteries but also of regularly developed P1-PCA and A1-ACA segments. However, unlike the M1-MCA, A2-ACA, and P2-PCA segments, the P1-PCA and A1-ACA segments show considerable variations of vessel diameter (Lang 2001).

Since catheter angiography was established in the 1950s it has been possible to evaluate the circle of Willis and collateral pathways in extra- and intracranial occlusive processes, as well as the regulatory circle of Willis function, in vivo (Fig. A5.149). Digital subtraction t e c h n i q u e s a n d s e l e c t i v e v e s s e l i m a g i n g i m p r o v e d t h e v i s ibility of collaterals and increased our understanding of their functional relevance. However, even in the advanced DSA techniques, a considerable amount of contrast has

which may alter the physiologic balance of intracranial perfusion pressure. Also, with the selective vessel imaging technique only parts of the cerebral circulation can be displayed at a time. Eﬀ ects of contrast dilution that can- not be avoided further restrict the evaluation of real ﬂ ow and therefore only the DSA technique permits assumptions with regard to the ﬂ ow direction and the strength of the blood ﬂ ow.

163Arterial Pathology

TAV

(cm/s)

max

150

Left CCA compression (2 min)

100

MCA-L

MCA-R

Time

Fig. A5.150 Bilateral TCD Doppler monitoring of the MCA during left CCA compression. Flow velocity of the right (green) and left (red) MCA are given as maximal time-averaged velocity values (TAV). Note the sharp drop in the left MCA ﬂ ow at beginning of the compression. Over a 2-minute period of compression, blood ﬂ ow of the left MCA recovers gradually, most signiﬁ cantly within the ﬁ rst 30 seconds, which can be explained by a gradually improving collateral recruitment. Note the physiologic “overshoot” in left MCA ﬂ ow on release of the compression.

The noninvasive techniques currently used to assess these issues are MRI and ultrasound. In MRI, the phase-contrast MRA technique can depict A1-ACA or PCoA ﬂ ow directions in patients with an ipsilateral ICA occlusion (Kluytmans et al 1999). However, this technique is time consuming and does not provide suﬃ cient information regarding the quantity or quality of collateral ﬂ ow, and hence has not yet become part of current diagnostic routines. In contrast, the frequently used TOFMRA is very fast. However, ﬂ ow direction is not displayed and there are some methodological limitations because of its ﬂ ow dependency. Normal communicating arteries with physiologic low ﬂ ow, or in cases of ICA occlusion with a turbulent ﬂ ow within the communicating arter- ies, may not be adequately depicted. Higher ﬁ eld strength increases the sensitivity. In a comparative study of DSA and 1.5-T TOF-MRA in a mixed group of patients with and without arterial occlusions, the PCoA was visualized with the MRI technique in 81% of cases with positive DSA ﬁ ndings in all of the patients (Patrux et al 1994). Using

7.0 T, the detection rate increases. A bilateral absence was seen in only 4.3% and a unilateral absence in 15.2% (Conijn et al 2009). The PCoA is a unique artery that forms a connection between the anterior and posterior cerebral circulation. Thus, in the case of a balanced blood supply anteriorly and posteriorly through the circle of Willis, the blood ﬂ ow through the PCoA can be very low if related to its diameter. A 16-detector-row CTA showed an overall agreement of 92.4% with DSA for the PCoA, ACoA, P1PCA, and A1-ACA. Subgroup analysis of the hypoplastic segments showed a sensitivity of 52.6% and a speciﬁ city of 98.2% (Han et al 2011). No systemic analysis has been published in stroke patients.

In comparison to the DSA technique, ultrasound permits a direct and real-time evaluation of the intracranial hemodynamic eﬀ ects of an extracranial arterial occlusion.

A clear advantage of the ultrasound technique compared with DSA is that it only observes the cerebral circulation without manipulating blood ﬂ ow by an injection of arti- ﬁ cial contrast. Provided that good insonation conditions are present, ﬂ ow waveforms and ﬂ ow velocities within the ACoA and PCoA in combination with the analysis of distal vessel segments makes it possible to assess the presence and the hemodynamic relevance of the communicating arteries in steno-occlusive disorders. In healthy individuals the communicating arteries are often diﬃ cult to visualize. The ACoA, with a length ranging from 0.1 to 3 mm ( Yasargil

1984) is too short to be directly shown by current ultrasound systems and shows no real ﬂ ow under physiologic conditions. The PCoA is also small, its diameter in 53% of cases reported to be less than 1 mm (Lang 2001). This, together with a frequently tortuous and basal course as well as the unfavorable angle of insonation, usually hinders PCoA detection under normal conditions. To assess patency and function of both communicating arteries in the absence of an occlusive process, a CCA compression test can be performed. Transient artiﬁ cial CCA occlusion over three to ﬁ ve heart cycles will, in the case of a functional ACoA, result in retrograde ipsilateral A1-ACA ﬂ ow. A functional PCoA under compression has been deﬁ ned as an ipsilateral ﬂ ow rise of the P1-PCA of at least 20%. Following these criteria a closed and therefore functional circle of Willis was detected in 29% of cases in an elderly arteriosclerotic population without stroke (Hoksbergen et al 2000b). A hypofunctional ACoA was found in 4% of cases and a hypofunctional PCoA in 61%, in 45% unilateral and 16% bilaterally (see Fig. A2.16). The same investigator group compared chronic stroke patients with controls. They reported higher incidences of functional impairment of the ACoA (33% versus 6%) and PCoA (57% versus 43%) (Hoksbergen et al 2003a). Interestingly, their ﬁ ndings indicate that a patent circle of Willis is not only of hemodynamic importance in extracranial vessel occlusions but might also be relevant for the wash-out of embolic material.

Although an elegant functional paradigm, the CCA compression test is not free from interpretation problems. The deﬁ nition of a functioning PCoA particularly has to be questioned because of the arbitrary chosen cut-oﬀ of a >20% P1-PCA ﬂ ow rise. In addition, it has to be kept in mind that the ultrasound detection of the P1-PCA may be diﬃ cult, particularly if TCD is used. The P1-PCA is a very short vessel segment with a mean length of 6 mm (range 3–9 mm; Lang 2001) and might also easily be confused with the nearby SCA or the proximal P2-PCA segment. Furthermore, a relatively brief compression does not automatically make it possible to draw conclusions regarding function after prolonged occlusion. It seems obvious that ﬁ rst-order collaterals will immediately respond to the altered pressure gradient; however, a collateral pathway via the communicating arteries may also start after more than three to

ﬁ ve heart cycles—minutes, or possibly even longer (Fig. A5.150) (Widder et al 1994). Considering this, the prev-

alence of functional communication arteries might even be higher than reported above. A compression of the CCA might lead to a thromboembolic complication in the atherosclerotic population and was reported in 2 of 380 examined patients, resulting in a stroke risk of 0.5%,

164 5 Vascular Pathology

and is therefore not recommended in routine ultrasound examinations (Mast et al 1993).

Although functional characteristics of the communicating arteries are easy to assess by ultrasound, no morphologic information can be obtained. Again, Hoksbergen and his group compared functional TCCS examinations and postmortem anatomic vessel ﬁ ndings. They found a threshold diameter of the communicating arteries for ﬁ rst-order collaterals of 0.4–0.6 mm, i.e., considerably lower than the previously assumed 1 mm, which derives mainly from anatomic observations. They reported a mean diameter of a functioning ACoA or PCoA of 1.1 mm (range 0.4–2 mm) and for a nonfunctioning ACoA or PCoA of 0.5 mm (range 0.3–0.7 mm). The lower cut-oﬀ of 0.4 mm is probably more valid for the ACoA, and the higher one of 0.6 mm for the PCoA as its length and the resulting increased resistance have to be taken into consideration (Hoksbergen et al 2000a).

Vessels of ~0 .5 mm dia mete r are usu ally no t vis ualiz ed by any of the current angiologic methods, particularly under physiologic circumstances in which the net ﬂ ow in these segments is low or even undulating. As soon as they serve as collaterals a mismatch between vessel diameter and required blood volume ﬂ ow develops which leads to a subsequent rise in ﬂ ow velocity (so-called “functional stenosis”), which is then rather easy to detect by ultrasound techniques.

Fetal-type Posterior Cerebral Artery

As mentioned, the communicating arteries can only work eﬀ ectively if the A1-ACA or P1-PCA is patent. A functionally relevant A1-ACA hypoplasia not allowing a cross-ﬂ ow in transient CCA occlusion is rare, occurring in only ~1% (Hoksbergen et al 2000b). However, variants of the P1-PCA are common, especially the fetal-type (FT)-PCA in which the PCA directly originates from the ICA without apparent connection to the BA (full type) or with a small vessel bridge, i.e., a hypoplastic P1-PCA (partial type). The discrimination from an FT-PCA with a strong PCoA is inconsistent. From a morphologic point of view the best way is to deﬁ ne a partial FT-PCA if the PCoA diameter exceeds the P1-PCA diameter, which has been reported in ~20% of hemispheres (Lang 2001, Saeki and Rhoton 1977). DSA is the best radiologic method to demonstrate potential connections between the anterior and posterior circulation. In a panangiographic study an exclusive PCA contrast ﬁ lling from the ICA was observed in 11% of hemispheres. In another 46% of hemispheres a combined supply via ICA and BA was found (Jongen et al 2002). An almost identical prevalence of 10% of full FT-PCA was reported in a DSA-correlated CTA study (van der Lugt et al 2004). MRA mainly uses morphological criteria considering the diameter of the target vessels to deﬁ ne an FT-PCA. Wide ranges were reported of a full FT-PCA ranging from 3% to 30% and of a partial FT-PCA ranging from 13% to 26%, highlighting diﬀ erences in deﬁ nitions and study populations as well as methodologic limitations (Jongen et al 2004, van Raamt et al 2006). No real CTA literature is available about this topic.

FT-PCA is also diﬃ cult to deﬁ ne with ultrasound methods. TCCS might, for example, fail to detect a small

hypoplastic P1-PCA segment because of its low net ﬂ ow. Diﬀ erentiation from the nearby SCA might also be prob- lematic. Applying the CCA compression test in 76 subjects and deﬁ ning FT-PCA as a ﬂ ow reduction or cessation in the PCA, this variant has been detected in 14% of subjects while no bilateral FT-PCA was reported (Hoksbergen et al 2000b). Alternatively, a diﬀ erentiation between normal and FT-PCA can also be achieved by a simple tap test. Using the latter technique, a similar prevalence of 17% for an FT-PCA has been reported (Siemieniec et al 2006). A diﬀ erentiation between a strong PCoA and an FT-PCA is usually not of relevance from a clinical point of view (for further reading on FT-PCA anatomy see Chapter 2, “Posterior Communicating Artery” under “Special Arterial Anatomy and Ultrasound Anatomy”).

Secondary Collaterals (Ophthalmic Artery and Leptomeningeal Collaterals)

Second-order collaterals are the OA and the leptomeningeal vessels in hemodynamically relevant steno-occlusive vessel disorders proximal to the communicating arteries. They can be considered as reserve systems that are only activated to compensate a relevant proximal vessel occlusion if the anterior and posterior communicating arteries are either insuﬃ ciently developed or not developed at all.

The OA connects the extra- and intracranial anterior circulation. Under physiologic conditions, in the normal type its blood supply mainly derives from the ICA. In 2.4% of cases, a partial blood supply occurs from the middle meningeal artery, a peripheral ECA branch merging from the maxillary artery. In 1.2% of cases an exclusive middle meningeal artery blood supply can be found (Hayreh and Dass 1962). In all of the above circumstances the physiologic blood ﬂ ow in the OA is cen- trifugal. In case of an OA collateral activation, which is only possible in an OA with ICA origin, the ﬂ ow direction reverses and the OA becomes a brain-supplying artery. Typ ic ally t he bl ood ﬂ ow then comes from the superﬁ cial temporal artery or facial artery via the supratrochlear artery to the OA. However, vessel ﬁ lling may also occur via the maxillary artery and ethmoidal arteries.

Recruited OA collaterals are easily depicted by DSA during selective ECA main stem or branch contrast injection (Fig. A5.151A). However, if the contrast is injected proximally, i.e., at the aortic arch or the CCA or only in the proximal ICA, an OA collateral may be missed because of contrast dilution. CTA and MRA usually fail to detect the OA but TCCS and TCD are optimally suited as they allow direct insonation of the vessel via the transorbital as well as the transtemporal approach. The assessment of waveform and ﬂ ow direction in particular allows evaluation of its relevance as a collateral vessel (for further details on OA anatomy, see Chapter 2, “Ophthalmic Artery” under “Special Arterial Anatomy and Ultrasound Anatomy”).

The last important potential collaterals are the leptomeningeal or pial arteries, the ﬁ nal segments of the MCA, ACA, and PCA, ﬁ rst described by Heubner in 1872 (see Fig. A2.15). In situations where there is a need the leptomeningeal arteries are able to activate and widen pre-existing anastomosis between all three vascular territories of the cerebrum, forming the so-called l e p t o m e n i n g e a l c o l l a t e r a l s ( L M C s ) ( Fig. A5.152 and

PcoA

165Arterial Pathology

Fig. A5.151 DSA. (A) Selective CCA injection, lateral view. ICA o c c l u s i o n ( a r r o w ) . C o l l a t e r a l ﬁ lling of the carotid siphon (arrowhead) via the retrograde OA (arrows) from the ECA. (B) Selective right VA injection, posteroanterior view. Left ICA occlusion. Collateral ﬁ lling of the MCA territory via PCA leptomeningeal collaterals (arrows). Note the prominent cortical PCA branch (anterior temporal artery) mainly distributing blood into the MCA territory (arrowhead).

Fig. A5.153). The anastomoses are usually end-to-end or candelabra-like (Vander Eecken 1959, Vander Eecken and Adams 1953). The regulatory mechanisms involved and the temporal patterns of development are still not well understood but a high inter-individual variability of these collaterals can be assumed (Liebeskind 2003). Anatomically, they may reach a diameter of up to 1 mm, the size of the normal pial arteries over the cerebral hemispheres (Brozici et al 2003). Their distribution, number, and size are variable. They are best developed between the MCA and ACA territory, less developed between the MCA and PCA, and only weakly developed between the ACA and PCA. Their activation represents a shifting of the vascular territories of the MCA, ACA, or PCA. Metabolic syndrome, hyperuricemia, and age have been found to be associated with poor leptomeningeal collateral status in patients with acute ischemic stroke, which may be explained by increasing vessel wall rigidity in these conditions (Brozici et al 2003, Menon et al 2013b).

It is important to note that the LMCs are secondary collaterals in extracranial steno-occlusive vessel disorders. In extracranial ICA occlusion—the prototype of extracranial occlusion—ﬁ rst-line collaterals are the ACoA and PCoA. Only if these fail are LMCs from the ACA and PCA as well as the OA activated, i.e., they are a sign of insuﬃ cient pri- mary collateral capacity (Hofmeijer et al 2002). In hemodynamically relevant steno-occlusive intracranial pathology, e.g., MCA occlusion, the communicating arteries and the OA cannot be activated, for anatomic reasons. Under these circumstances the ACA and PCA LMCs are the only vessels that may compensate for the occlusion. Therefore, in intracranial occlusions (with the exception of ICA occlusion proximately to the communicating arteries), the LMC are the primary (and only) collaterals and determine the prognosis of the patient (Liebeskind et al 2011). In the best case the LMCs are able to maintain the perfusion of the whole MCA territory, as has been shown in a cadaver study case with reported MCA main stem occlusion (Nishida et al

Fig. A5.152 Schematic of leptomeningeal collaterals in proximal M1-MCA occlusion. In occlusion distal of the communicating a r t e r i e s t h e l e p t o m e n i n g e a l a n a s t o m o s e s p r e s e n t t h e o n l y c o l l a t eral input. In our example leptomeningeal collaterals are activated from the ACA (red) and PCA (blue). (Adapted from Vander Eecken

1959.)

Fig. A5.153 Corrosion preparation of a leptomeningeal anastomosis between two leptomeningeal M4-MCA branches (arrows). (Adapted from Vander Eecken 1959.)

2000). This, however, requires rapid LMC activation, which ﬁ nally determines the extent of the hypoperfusion and subsequently the area of infarction. Within the posterior circulation LMCs may also be activated between the three cerebellar arteries (see Fig. A5.141).

LMCs can be studied by DSA, CTA, MRI, and MRA as well

by sonographic methods. Despite their importance, it remains diﬃ cult to grade the eﬃ cacy of collateral ﬂ ow and to compare the diﬀ erent methods especially in intracranial proximal vessel occlusion (McVerry et al 2012). DSA imaging of LMCs is easily achieved, particularly within the early and late arterial and capillary phases of the contrast passage. The early arterial phase directly visualizes the feeding vessels, which may be particularly prominent in the PCA and ACA territory in occlusive conditions of the MCA or ICA (Fig. A5.151B and Fig. A5.154). The late arterial and capil- lary phases usually allow a clear mapping of the territories

166 5 Vascular Pathology

ACA

MCA

PCA

ACA

Fig. A5.154 (A) Schematic of the normal distribution of vascular ter- ritories, coronal plane. (B) Schematic of shifted vascular territories toward the ACA and PCA caused by MCA occlusion. (C) DSA, selective left ICA ﬁ lling, posteroanterior view: M1-MCA occlusion (arrow). Note the normal borders of the ACA territory on the right side (thin dashed line) and the shifting of the left ACA territory (thick dashed line) corresponding to the theoretical considerations shown under B.

A B

PCA

Fig. A5.155 DSA and schematic of collaterals in MCA occlusion. (A,B) DSA, selective ICA ﬁ lling, posteroanterior view. (A) Early ar- terial phase: M1-MCA occlusion (arrow). (B) Late arterial/capillary phase: Note the retrograde ﬁ lling of insular MCA branches (arrows) via ACA leptomeningeal collaterals (curved arrow). (C) Schematic summarizing ﬁ ndings of the case shown in A and B.

Fig. A5.156 DSA, composite image, left and right selective ICA injection late arterial phase, posteroanterior view. (A) Bilateral A1-ACA occlusion (arrows). Note the ﬁ lling of the ACA territory via LMC from the MCA territory (arrowheads). (B) Bilateral A2-ACA occlusion (arrow). As in the case shown in A, there is ﬁ lling of the ACA territory via LMC from the MCA territory (arrowheads).

supplied by the LMCs. In addition, the capillary phase of the normal perfusion of brain parenchyma demonstrates the extent of the centripetal collateral ﬁ lling. Under optimal circumstances even a proximal main stem vessel might be ﬁ lled in retrograde via the LMC (Fig. A5.155). The magnitude of centripetal ﬁ lling can be graded using diﬀ erent systems (McVerry et al 2012). One system uses a scoring system between 1 and 5, where a score of 5 means little or no significant reconstitution of the occluded vessel territory and a score of 1 indicates that the distal portion of the occluded vessel is reﬁ lled (Christoforidis et al 2005). In occlusion of the PCA LMCs starts from the MCA and ACA and in occlusion of the ACA leptomeningeal activation comes from cortical

Fig. A5.157 DSA, right selective ICA injection, late arterial phase, posteroanterior view. Small image shows a distal M1-MCA occlusion (arrow) and a prominent early temporal M1-MCA branch (arrowhead). The large image shows a normal ACA territory border on the left side (thin dashed line) and the shifting of the right ACA territory into the MCA territory (thick dashed line) indicating LMC activation via the ACA. Additionally, the early temporal MCA branch also participates in forming a LMC MCA-MCA network (arrows).

branches of the MCA and PCA (Fig. A5.156). Leptomeningeal anastomoses can also build up between cortical branches of one vessel territory (Fig. A5.157).

In MRA analysis, LMCs can be indirectly assessed. U s i n g t h e ﬂ ow-sensitive TOF-MRA, the signal intensity of the vessels involved in leptomeningeal collateralization appear slightly stronger and more distal vessel segments are visible, both indicating a higher blood ﬂ ow (Ichijo et al 2013, Uemura et al 2004) (see Fig. A5.88). Further collateral signs on MRI are hyperintense leptomeningeal vessels on FLAIR (K.Y. Lee et al 2009). Abnormal vessels on T2* imaging, probably caused by deoxygenated blood in activated collaterals, may be also

167Arterial Pathology

Fig. A5.158 Schematic of the two main types of collateral ﬂ ow via communicating arteries in proximal ICA occlusion. (A) Crossﬂ ow from the contralateral side via contralateral A1-ACA, ACoA, r e t r o g r a d e i p s i l a t e r a l A 1 - A C A i n t o t h e i p s i l a t e r a l M C A t e r r i t o r y . (B) Collateral ﬂ ow from the ipsilateral P1-PCA via the PCoA into the ipsilateral MCA territory. Combinations of both patterns are possible.

be indicative of good LMCs and a good prognosis (Hermier et al 2005). The functionality of LMCs can also be well evaluated by assessment of the MRI perfusion sequences. For example, in MCA occlusion, the size of the perfusion deﬁ cit indirectly correlates with the quality of LMC from the ACA and PCA. In case of well-functioning collaterals, MTT values are low and the cerebral blood volume is only slightly raised (Kluytmans et al 1999). Arterial spin-labeling MR has also been used for LMC grading (Chng et al 2008, Sallustio et al 2008).

Even unenhanced CT is known to have a good correlation with LMC grade on DSA (Choi et al 2011). The Alberta Stroke Program Early CT Score (ASPECTS) can be used to analyze unenhanced CT scans for hypoattenuation in 10 deﬁ ned areas of the MCA territory (Barber et al 2000). The ASPECTS on contrast-enhanced CT or CTA source images correlates even better with baseline stroke severity than the basic ASPECTS (Bhatia et al 2011). In proximal occlusions a retrograde ﬁ lling of the leptome- ningeal arteries up to the occlusion site can be assumed. In distal occlusion LMCs can be evaluated by the strength of contrast enhancement in the peripheral arteries. CT p e r f u s i o n a d d s f u r t h e r i n s i g h t s i n t o ﬂ ow direction and the amount of LMC (Mortimer et al 2013, Tan et al 2007). Using standard single time-frame CTA, the LMC status may be underestimated in patients with large-vessel occlusion because of delayed contrast arrival and slower ﬁ lling of collaterals which then may not become visible. Analyzing late CTA images, derived from CT perfusion studies (timing-invariant CTA) good LMCs were seen in 84% of cases—signiﬁ cantly higher than standard CTA, which yielded only 49% (Smit et al 2013). A time-fused maximum intensity projection (tMIP) approach was shown to best depict collateral ﬂ ow and the authors hypothesized that the total extent of collateral ﬂ ow, rather than the ve- locity of collateral ﬁ lling, will predict the clinical outcome (Frölich et al 2014). Dynamic information can be gathered with modern 320-detector-row CT scanners, which generate time-resolved cerebral angiograms from skull base

to vertex. Unlike DSA, this technique makes it possible to visualize pial arterial ﬁ lling in all vascular territories. In 25 patients with M1-MCA and/or ICA occlusions a dominant PCA to MCA leptomeningeal collateral ﬂ ow was ob- served using this technique (Menon et al 2013a).

Ultrasound allows excellent assessment of LMC function. In case of LMC activation, ﬂ ow velocities within the supplying main stem arteries will be raised. In case of an MCA occlusion, these are the ipsilateral A1-ACA, P2- and P3-PCA; in case of an A1-ACA occlusion the ipsilateral M1-MCA, P2- and P3-PCA as well as the contralateral A1-ACA. The latter may be possible if a patent ACoA is present. A similar activation may occur in M1-MCA occlusion in ipsilateral A1-ACA hypo- or aplasia. Finally, in PCA occlusion, ﬂ ow velocities within the ipsilateral M1- MCA as well as the ipsilateral A1-ACA may be increased. In case of extracranial ICA occlusion mainly the PCA may serve as a LMC pathway, especially if the communicating arteries are nonfunctioning. Some cortical branches may be directly be studied by ultrasound, but their analysis is not yet part of routine TCCS. PCA branches like the anterior temporal and the occipitotemporal artery may be particularly strong and can readily be visualized in MCA occlusion (for further details on PCA branch anatomy, see Chapter 2, “Posterior Cerebral Artery” under “Special Arterial Anatomy and Ultrasound Anatomy”). Activation of the contralateral A1-ACA in LMC may occur in ipsilateral ICA occlusion via the ACoA in cases with ipsilateral A1-ACA aplasia or marked A1-ACA hypoplasia. Analysis of ﬂ ow asymmetry for evaluation of LMC activation in the A1- and A2-ACA as well as in the P1-PCA is limited because of their high anatomic variability. In contrast, side-to-side comparison in the always-symmetrical P2PCA segments is worthwhile. Here, provided that the insonation angle is respected, a ﬂ ow diﬀ erence >50% clearly indicates LMC activation while a diﬀ erence >30% can be considered highly suspicious.

Intracranial Collateral Pathways in ICA Occlusive Processes

Primary Collaterals (ACoA and PCoA)

In extracranial ICA occlusion, involvement of the ACoA via retrograde A1-ACA (cross-ﬂ ow) is seen in up to 80% of cases and activation of the PCoA can be seen in 70% of cases (Demchuk et al 2000b, Henderson et al 2000) (Fig. A5.158). If the diameter of both communicating arteries is too small for the required blood ﬂ ow, they will demonstrate raised ﬂ ow velocities and turbulence (func- tional stenosis) which is hemodynamically identical to a real stenosis—i.e., in the intracranial downstream vessels a so-called poststenotic ﬂ ow pattern or low-resistance ﬂ ow signal will be present, its magnitude depending on the diameter of the communicating artery. The post stenotic ﬂ ow pattern is characterized by a reduced ﬂ ow velocity (corresponding to a reduced blood ﬂ ow), a delayed systol- ic ﬂ ow rise (caused by a small-diameter communicating artery), and a raised diastolic ﬂ ow component, the last being attributable to a compensatory dilatation of the peripheral resistance vessels (see also Fig. A5.43, Fig. A5.44,

Fig. A5.45). In a large TCD study of 114 symptomatic and

168 5 Vascular Pathology

A1 contralateral

A1 ipsilateral M1 ipsilateral

Fig. A5.159 Left: Left proximal ICA occlusion. (A) DSA, selective right ICA ﬁ lling, posteroanterior view. Cross-ﬂ ow via right A1-ACA, ACoA (arrow), left A1-ACA into the left MCA territory. (B) TCCS, transtemporal approach, axial midbrain plane (left-sided insonation). Color-mode image demonstrates the red-coded retrograde A1-ACA ﬂ ow (arrow). Right: Corresponding Doppler spectra of the right, contralateral A1-ACA (strong antegrade ﬂ ow), the ACoA (raised ﬂ ow velocity and turbulence), the ipsilateral A1-ACA (ret- rograde ﬂ ow) and the ipsilateral M1-MCA (mildly reduced ﬂ ow ve- locity). Note the transient oscillations within the left MCA Doppler spectrum on digital tapping of the right extracranial ICA (arrows).

ACoA

asymptomatic patients with a >80% ICA stenosis, 54% of patients demonstrated a poststenotic ﬂ ow pattern which the authors called a “blunted” waveform. Symptomatic patients presented this pattern signiﬁ cantly more often than asymptomatic patients (80% versus 37%, respectively) (Hartmann et al 2000).

In a small TCD study including 17 patients with proximal ICA occlusion a poststenotic ﬂ ow pattern was seen in 67% of cases (Demchuk et al 2000b). This means that one-third of these patients did not show any ﬂ ow pro- ﬁ le alterations within the downstream vessels, indicating good functioning of primary collateral pathways.

Whenever a cross-ﬂ ow via the ACoA is present, the A1-ACA of the unaﬀ ected side shows raised ﬂ ow veloci- ties as it has to provide the blood supply for at least both ACA territories and often also for the contralateral MCA territory. If its ﬂ ow velocity is clearly higher than that of the ipsilateral MCA and ACoA, a cross-ﬂ ow can be as- sumed even if a direct visualization of the retrograde A1ACA on the side of the occlusion is diﬃ cult (Fig. A5.159). Baumgartner and coworkers reported in a DSA-correlated study in 78 patients with >70% stenosis- or occlusion-induced ACoA cross-ﬂ ow, a peak systolic ﬂ ow velocity of 141 ± 36 cm/s within the A1-ACA contralateral to the occlusive process, and an M1-MCA velocity of 103 ± 27 cm/s on the same side. In comparison, MCA ﬂ ow velocities on the occluded side were lower (79 ± 24 cm/s) (Baumgartner et al 1996). The ACoA in these circumstances may become apparent as a functional stenosis. If a turbulent ﬂ ow is also seen in the retrograde A1-ACA, transmission of turbulence from the ACoA or a functional stenosis of the A1-ACA itself indicating (relative) hypoplasia may be the underlying cause. The diameter of the ACoA and A1-ACA determines the MCA waveform on the side of the occlu-

A B

Fig. A5.160 Diﬀ erent quality of collateral blood ﬂ ow via the ACoA in extracranial left ICA occlusion. Top: DSA, right ICA injection, pos- teroanterior view. Bottom: Corresponding Doppler waveform of the MCA ipsilateral to the occlusion. (A) Optimal collateral ﬂ ow with nearly simultaneous contrast ﬁ lling of both MCA territories and a l m o s t n o r m a l M C A w a v e f o r m r e v e a l i n g o n l y a m i l d e l e v a t e d d i a s tolic ﬂ ow. (B) Impaired collateral ﬂ ow with delayed MCA contrast ﬁ lling on the side of the occlusion and a marked poststenotic ﬂ ow pattern in the MCA mainly with an elevated diastolic ﬂ ow but also mild delayed systolic upraise. Note the assumed diﬀ erent diameter of the ACoA, explaining the divergent MCA ﬂ ow signals.

ACoA ACoA

A1 A1

sion which may appear almost normal, poststenotic, or in the worst case venous-like. The DSA appearance of this impairment is a delayed contrast ﬁ lling on the side of the occlusion (Fig. A5.160). TOF-MRA will show reduced signal intensity in the aﬀ ected MCA as an equivalent of a poststenotic ﬂ ow (Fig. A5.161). A DSA-correlated study in 117 patients revealed a high diagnostic accuracy of crossﬂ ow detection by TCCS, provided that good insonation conditions were present. If the ACoA cross-ﬂ ow is deﬁ ned as a retrograde A1-ACA ﬂ ow on the side of the occlusion, or as an M1-MCA ﬂ ow reduction on the side of the oc- clusion on contralateral CCA compression, the sensitivity, speciﬁ city, and positive and negative predictive values are 98%, 100%, 100%, and 98%, respectively (Baumgartner et al 1997a). CCA compression should no longer be performed in routine ultrasound examination especially in patients with vascular risk factors. In case of doubt about the presence of an ACoA cross-ﬂ ow, extracranial tapping may help to identify the collateral ﬂ ow pattern. If digital tapping of the contralateral submandibular ICA leads to a distinct oscillation eﬀ ect within the ipsilateral MCA, a cross-ﬂ ow is highly likely.

If a collateral ﬂ ow occurs via the ipsilateral PCoA, the P1-PCA has raised ﬂ ow velocities as it then also has to provide the blood supply to parts or all of the total ipsilateral anterior circulation. The post-communicating PCA segments may then reveal completely normal ﬂ ow veloc- ities. If not, additional leptomeningeal collateralization must be present (Fig. A5.162 and Fig. A5.163). In the study by Baumgartner and coworkers (1996), the peak systolic P1-PCA ﬂ ow velocities were 107 ± 31 cm/s on the side of the occlusive process and 69 ± 13 cm/s on the contralateral side. Often the PCoA is then easy to visualize in color mode because of the raised ﬂ ow velocities. Also, functional

<<< < Предыдущая 7 8 9 10 11 12 13 14 15 16 17 1819 / 5019 20 21 22 23 24 25 26 27 28 29 30 31 > Следующая >>>

Соседние файлы в папке Библиотека им академика М.И. Перельмана

#
30.08.202663 Мб0Книга_5771_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202658 Мб0Книга_5772_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202658 Мб0Книга_5773_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202657 Мб0Книга_5774_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202656 Мб0Книга_5775_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202653 Мб0Книга_5776_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202651 Мб0Книга_5777_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202648 Мб0Книга_5778_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202642 Мб0Книга_5779_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202678 Мб0Книга_578_Библиотеки_им_академика_М_И_Перельмана.pdf
#
30.08.202642 Мб0Книга_5780_Библиотеки_им_академика_М_И_Перельмана.pdf